Angiogenesis - Knowledge (XXG)

713:(basic FGF) consists to date of at least 22 known members. Most are single-chain peptides of 16-18 kDa and display high affinity to heparin and heparan sulfate. In general, FGFs stimulate a variety of cellular functions by binding to cell surface FGF-receptors in the presence of heparin proteoglycans. The FGF-receptor family is composed of seven members, and all the receptor proteins are single-chain receptor tyrosine kinases that become activated through autophosphorylation induced by a mechanism of FGF-mediated receptor dimerization. Receptor activation gives rise to a signal transduction cascade that leads to gene activation and diverse biological responses, including cell differentiation, proliferation, and matrix dissolution, thus initiating a process of mitogenic activity critical for the growth of endothelial cells, fibroblasts, and smooth muscle cells. FGF-1, unique among all 22 members of the FGF family, can bind to all seven FGF-receptor subtypes, making it the broadest-acting member of the FGF family, and a potent mitogen for the diverse cell types needed to mount an angiogenic response in damaged (hypoxic) tissues, where upregulation of FGF-receptors occurs. FGF-1 stimulates the proliferation and differentiation of all cell types necessary for building an arterial vessel, including endothelial cells and smooth muscle cells; this fact 1111:: the production of new collateral vessels to overcome the ischemic insult. A large number of preclinical studies have been performed with protein-, gene- and cell-based therapies in animal models of cardiac ischemia, as well as models of peripheral artery disease. Reproducible and credible successes in these early animal studies led to high enthusiasm that this new therapeutic approach could be rapidly translated to a clinical benefit for millions of patients in the Western world with these disorders. A decade of clinical testing both gene- and protein-based therapies designed to stimulate angiogenesis in underperfused tissues and organs, however, has led from one disappointment to another. Although all of these preclinical readouts, which offered great promise for the transition of angiogenesis therapy from animals to humans, were in one fashion or another, incorporated into early stage clinical trials, the FDA has, to date (2007), insisted that the primary endpoint for approval of an angiogenic agent must be an improvement in exercise performance of treated patients. 865:. There have been many studies conducted that have served to determine consequences of the Delta-like Ligand 4. One study in particular evaluated the effects of Dll4 on tumor vascularity and growth. In order for a tumor to grow and develop, it must have the proper vasculature. The VEGF pathway is vital to the development of vasculature that in turn, helps the tumors to grow. The combined blockade of VEGF and Dll4 results in the inhibition of tumor progression and angiogenesis throughout the tumor. This is due to the hindrance of signaling in endothelial cell signaling which cuts off the proliferation and sprouting of these endothelial cells. With this inhibition, the cells do not uncontrollably grow, therefore, the cancer is stopped at this point. if the blockade, however, were to be lifted, the cells would begin their proliferation once again. 1021: 1201:'s research findings were compiled. In his study, Hunter observed the growth process of new blood vessels in rabbits. However, he did not coin the term "Angiogenesis," which is now widely used by scholars. Hunter also erroneously attributed the growth process of new blood vessels to the effect of an innate vital principle within the blood. The term "angiogenesis" is believed to have emerged not until the 1900s. The inception of modern angiogenesis research is marked by Judah Folkman's report on the pivotal role of angiogenesis in tumor growth. 94: 1152:

capillaries allows the network to deliver more nutrients in the same amount of time. A greater number of capillaries also allows for greater oxygen exchange in the network. This is vitally important to endurance training, because it allows a person to continue training for an extended period of time. However, no experimental evidence suggests that increased capillarity is required in endurance exercise to increase the maximum oxygen delivery.

732:); however, it is less potent than FGF-1. As well as stimulating blood vessel growth, aFGF (FGF-1) and bFGF (FGF-2) are important players in wound healing. They stimulate the proliferation of fibroblasts and endothelial cells that give rise to angiogenesis and developing granulation tissue; both increase blood supply and fill up a wound space/cavity early in the wound-healing process. 1052:

away the biological end products secreted by rapidly dividing cancer cells. In either case, angiogenesis is a necessary and required step for transition from a small harmless cluster of cells, often said to be about the size of the metal ball at the end of a ball-point pen, to a large tumor. Angiogenesis is also required for the spread of a tumor, or

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intravenous, intra-arterial, or intramuscular routes of protein administration are not always as effective, as the therapeutic protein may be metabolized or cleared before it can enter the target tissue. Cell-based pro-angiogenic therapies are still early stages of research, with many open questions regarding best cell types and dosages to use.

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produces network changes that allow for a large increase in the amount of total flow in a network, angiogenesis causes changes that allow for greater nutrient delivery over a long period of time. Capillaries are designed to provide maximum nutrient delivery efficiency, so an increase in the number of

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enzymes from the vasculature. These enzymes target a particular point on the blood vessel and cause a pore to form. This is the point where the new blood vessel will grow from. The reason tumour cells need a blood supply is because they cannot grow any more than 2-3 millimeters in diameter without an

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cells. Binding to VEGF receptor-2 (VEGFR-2) starts a tyrosine kinase signaling cascade that stimulates the production of factors that variously stimulate vessel permeability (eNOS, producing NO), proliferation/survival (bFGF), migration (ICAMs/VCAMs/MMPs) and finally differentiation into mature blood

1056:. Single cancer cells can break away from an established solid tumor, enter the blood vessel, and be carried to a distant site, where they can implant and begin the growth of a secondary tumor. Evidence now suggests the blood vessel in a given solid tumor may, in fact, be mosaic vessels, composed of 943:

in the body may help combat such diseases. The presence of blood vessels where there should be none may affect the mechanical properties of a tissue, increasing the likelihood of failure. The absence of blood vessels in a repairing or otherwise metabolically active tissue may inhibit repair or other

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Chien CC, Kempson IM, Wang CL, Chen HH, Hwu Y, Chen NY, et al. (May–June 2013). "Complete microscale profiling of tumor microangiogenesis: a microradiological methodology reveals fundamental aspects of tumor angiogenesis and yields an array of quantitative parameters for its characterization".

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Angiogenesis of vessels from the host body into an implanted tissue engineered constructs is essential. Successful integration is often dependent on thorough vascularisation of the construct as it provides oxygen and nutrients and prevents necrosis in the central areas of the implant. PDGF has

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The modern clinical application of the principle of angiogenesis can be divided into two main areas: anti-angiogenic therapies, which angiogenic research began with, and pro-angiogenic therapies. Whereas anti-angiogenic therapies are being employed to fight cancer and malignancies, which require an

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By contrast, pro-angiogenic protein therapy uses well-defined, precisely structured proteins, with previously defined optimal doses of the individual protein for disease states, and with well-known biological effects. On the other hand, an obstacle of protein therapy is the mode of delivery. Oral,

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can induce capillary growth into the tumor, which some researchers suspect supply required nutrients, allowing for tumor expansion. Unlike normal blood vessels, tumor blood vessels are dilated with an irregular shape. Other clinicians believe angiogenesis really serves as a waste pathway, taking

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production of VEGF receptors 1 and 2. The increase in receptor production means muscle contractions could cause upregulation of the signaling cascade relating to angiogenesis. As part of the angiogenic signaling cascade, NO is widely considered to be a major contributor to the angiogenic response

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is a mode of angiogenesis, considered to be the opposite of intussusceptive angiogenesis, where capillaries fuse, or coalesce, to make a larger bloodvessel, thereby increasing blood flow and circulation. Coalescent angiogenesis has extended out of the domain of embryology. It is assumed to play a

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Quantifying vasculature parameters such as microvascular density has various complications due to preferential staining or limited representation of tissues by histological sections. Recent research has shown complete 3D reconstruction of tumor vascular structure and quantification of vessel

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The mechanism of blood vessel formation by angiogenesis is initiated by the spontaneous dividing of tumor cells due to a mutation. Angiogenic stimulators are then released by the tumor cells. These then travel to already established, nearby blood vessels and activates their endothelial cell

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studies clearly demonstrate that VEGF is a potent stimulator of angiogenesis because, in the presence of this growth factor, plated endothelial cells will proliferate and migrate, eventually forming tube structures resembling capillaries. VEGF causes a massive signaling cascade in

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Sprouting angiogenesis was the first identified form of angiogenesis and because of this, it is much more understood than intussusceptive angiogenesis. It occurs in several well-characterized stages. The initial signal comes from tissue areas that are devoid of vasculature. The

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Angiogenesis represents an excellent therapeutic target for the treatment of cardiovascular disease. It is a potent, physiological process that underlies the natural manner in which our bodies respond to a diminution of blood supply to vital organs, namely

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Goto F, Goto K, Weindel K, Folkman J (November 1993). "Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels".

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established blood supply which is equivalent to about 50-100 cells. Certain studies have indicated that vessels formed inside the tumor tissue are of higher irregularity and bigger in size, which is as well associated with poorer prognosis.

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There are still serious, unsolved problems related to gene therapy. Difficulties include effective integration of the therapeutic genes into the genome of target cells, reducing the risk of an undesired immune response, potential toxicity,

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that is noted in these areas causes the tissues to demand the presence of nutrients and oxygen that will allow the tissue to carry out metabolic activities. Because of this, parenchymal cells will secrete vascular endothelial growth factor

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because inhibition of NO significantly reduces the effects of angiogenic growth factors. However, inhibition of NO during exercise does not inhibit angiogenesis, indicating there are other factors involved in the angiogenic response.

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for growth of the vessel lumen. Finally, the core is fleshed out with no alterations to the basic structure. Intussusception is important because it is a reorganization of existing cells. It allows a vast increase in the number of

751:, although the results were more pronounced with VEGF. Upregulation of VEGF is a major component of the physiological response to exercise and its role in angiogenesis is suspected to be a possible treatment in vascular injuries. 1003:

related to the viral vectors used in implanting genes and the sheer complexity of the genetic basis of angiogenesis. The most commonly occurring disorders in humans, such as heart disease, high blood pressure, diabetes and

948:, are the result of failure or insufficient blood vessel formation and may be treated by a local expansion of blood vessels, thus bringing new nutrients to the site, facilitating repair. Other diseases, such as age-related 728:) is the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures, thus promoting angiogenesis. FGF-2 is a more potent angiogenic factor than VEGF or PDGF ( 4024: 1071:

Endothelial cells have long been considered genetically more stable than cancer cells. This genomic stability confers an advantage to targeting endothelial cells using antiangiogenic therapy, compared to

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in the context of the overall cellular microenvironment may play a vital role in their utility. It may be necessary to present these proteins in a way that mimics natural signaling events, including the

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Arrabi N, Torabi M, Fassihi A, Ghasemi F (2024). "Identification of potential vascular endothelial growth factor receptor inhibitors via tree-based learning modeling and molecular docking simulation".

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These failures suggested that either these are the wrong molecular targets to induce neovascularization, that they can only be effectively used if formulated and administered correctly, or that their

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Haas TL, Milkiewicz M, Davis SJ, Zhou AL, Egginton S, Brown MD, et al. (October 2000). "Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle".

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acting on capillaries to cause angiogenesis, although current knowledge suggests that increased muscle contractions may increase angiogenesis. This may be due to an increase in the production of

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McDougall SR, Anderson AR, Chaplain MA (August 2006). "Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies".

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Hellström M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, et al. (February 2007). "Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis".

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vessels. Mechanically, VEGF is upregulated with muscle contractions as a result of increased blood flow to affected areas. The increased flow also causes a large increase in the

1036:. However, tumors need a dedicated blood supply to provide the oxygen and other essential nutrients they require in order to grow beyond a certain size (generally 1–2 mm). 4010: 2865:"VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation" 968:. One of the first applications of pro-angiogenic methods in humans was a German trial using fibroblast growth factor 1 (FGF-1) for the treatment of coronary artery disease. 2397:

Gavin TP, Robinson CB, Yeager RC, England JA, Nifong LW, Hickner RC (January 2004). "Angiogenic growth factor response to acute systemic exercise in human skeletal muscle".

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to split a single vessel in two. There are four phases of intussusceptive angiogenesis. First, the two opposing capillary walls establish a zone of contact. Second, the

1008:, are most likely caused by the combined effects of variations in many genes, and, thus, injecting a single gene may not be significantly beneficial in such diseases. 1598:

Milosevic V, Edelmann RJ, Fosse JH, Östman A, Akslen LA (2022). "Molecular Phenotypes of Endothelial Cells in Malignant Tumors". In Akslen LA, Watnick RS (eds.).

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as cells migrate to the site of angiogenesis. Sprouting occurs at a rate of several millimeters per day, and enables new vessels to grow across gaps in the

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characterized by either poor vascularisation or abnormal vasculature. Application of specific compounds that may inhibit or induce the creation of new

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Torabi M, Yasami-Khiabani S, Sardari S, Ghasemi F (2024). "Identification of new potential candidates to inhibit EGF via machine learning algorithm".

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Adair TH, Montani JP. Angiogenesis. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Chapter 1, Overview of Angiogenesis. Available from:

3135:"The Application of Artificial Intelligence and Drug Repositioning for the Identification of Fibroblast Growth Factor Receptor Inhibitors: A Review" 488: 2483:

Lloyd PG, Prior BM, Yang HT, Terjung RL (May 2003). "Angiogenic growth factor expression in rat skeletal muscle in response to exercise training".

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Kraus RM, Stallings HW, Yeager RC, Gavin TP (April 2004). "Circulating plasma VEGF response to exercise in sedentary and endurance-trained men".

1172:, causing loss of vision. Anti-angiogenic drugs targeting the VEGF pathways are now used successfully to treat this type of macular degeneration 1060:

and tumor cells. This mosaicity allows for substantial shedding of tumor cells into the vasculature, possibly contributing to the appearance of

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Khurana R, Simons M (April 2003). "Insights from angiogenesis trials using fibroblast growth factor for advanced arteriosclerotic disease".

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in the peripheral blood of patients with malignancies. The subsequent growth of such metastases will also require a supply of nutrients and

3322:"Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases" 1020: 242:

and form solid sprouts connecting neighboring vessels. The cells that are proliferating are located behind the tip cells and are known as

743:(VEGF) has been demonstrated to be a major contributor to angiogenesis, increasing the number of capillaries in a given network. Initial 896:

receptor binding at endothelial cells. The relative expression levels of SEMA3s and VEGF-A may therefore be important for angiogenesis.

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studies demonstrated bovine capillary endothelial cells will proliferate and show signs of tube structures upon stimulation by VEGF and

1501: 265:. It is markedly different from splitting angiogenesis because it forms entirely new vessels as opposed to splitting existing vessels. 4267: 1040: 988: 740: 718: 425: 392:

Chemical stimulation of angiogenesis is performed by various angiogenic proteins e.g. integrins and prostaglandins, including several

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Bagri A, Kouros-Mehr H, Leong KG, Plowman GD (March 2010). "Use of anti-VEGF adjuvant therapy in cancer: challenges and rationale".

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and cells to penetrate into the lumen. Third, a core is formed between the 2 new vessels at the zone of contact that is filled with

4098: 2816:"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor" 480: 376:

Mechanical stimulation of angiogenesis is not well characterized. There is a significant amount of controversy with regard to

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Thurston G (October 2003). "Role of Angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis".

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to escape into the interstitial matrix as seen in sprouting angiogenesis. Inhibition of MMPs prevents the formation of new

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Overexpression of VEGF causes increased permeability in blood vessels in addition to stimulating angiogenesis. In wet

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form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during

2765:"Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits tumor progression and angiogenesis" 2198:

Blaber M, DiSalvo J, Thomas KA (February 1996). "X-ray crystal structure of human acidic fibroblast growth factor".

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Flamme I, Frölich T, Risau W (November 1997). "Molecular mechanisms of vasculogenesis and embryonic angiogenesis".

1240: 1250: 862: 3902: 861:(Dll4) is a protein with a negative regulatory effect on angiogenesis. Dll4 is a transmembrane ligand, for the 827: 702: 696: 415: 136:, although discussions are not always precise (especially in older texts). The first vessels in the developing 64: 2348:"Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke" 4228: 4161: 3694:"Platelet-derived growth factor stabilises vascularisation in collagen-glycosaminoglycan scaffolds in vitro" 961: 359: 354: 207: 117: 1164:, VEGF causes proliferation of capillaries into the retina. Since the increase in angiogenesis also causes 341:. This is especially important in embryonic development as there are not enough resources to create a rich 4223: 4113: 3915: 2207: 1115: 1061: 1005: 911: 905: 676:

Modulates endothelial cell adhesion, migration, proliferation and apoptosis. Alters vascular permeability

164: 93: 76: 952:, may be created by a local expansion of blood vessels, interfering with normal physiological processes. 4398: 4233: 4143: 3496:

Mikalsen LT, Dhakal HP, Bruland ØS, Naume B, Borgen E, Nesland JM, Olsen DR (2013-10-11). Aoki I (ed.).

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Promotes proliferation & differentiation of endothelial cells, smooth muscle cells, and fibroblasts

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Segarra M, Williams CK, Sierra Mde L, Bernardo M, McCormick PJ, Maric D, et al. (September 2008).

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Stegmann TJ, Hoppert T, Schneider A, Gemeinhardt S, Köcher M, Ibing R, Strupp G (September 2000). "".

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Lobov IB, Renard RA, Papadopoulos N, Gale NW, Thurston G, Yancopoulos GD, Wiegand SJ (February 2007).

4103: 3509: 3193: 3015: 2972: 2921: 2672: 2617: 2101: 2042: 1255: 1161: 949: 847: 663: 608: 494: 329: 2212: 2090:"Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke" 175:, who described tumors as "hot and bloody," illustrating that, at least for many tumor types, flush 4069: 1888:

Prior BM, Yang HT, Terjung RL (September 2004). "What makes vessels grow with exercise training?".

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Lenzi P, Bocci G, Natale G (April 2016). "John Hunter and the origin of the term "angiogenesis"".

778:, Ang1 and Ang2, are required for the formation of mature blood vessels, as demonstrated by mouse 4377: 4341: 4108: 4059: 4034: 3959: 3829: 3776: 3723: 3447:

Milosevic V, Edelmann RJ, Winge I, Strell C, Mezheyeuski A, Knutsvik G, et al. (July 2023).

3240: 3074: 2945: 2845: 2696: 2586: 2543: 2465: 2422: 2375: 2248:

Stegmann TJ (December 1998). "FGF-1: a human growth factor in the induction of neoangiogenesis".

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consists of a population of rapidly dividing and growing cancer cells that progressively accrues

473: 246:. The proliferation of these cells allows the capillary sprout to grow in length simultaneously. 152: 133: 113: 2606:"Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting" 214:

present in pre-existing blood vessels. Second, the activated endothelial cells, also known as

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and nutrients to proliferate, pro-angiogenic therapies are being explored as options to treat

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Nitzsche B, Rong WW, Goede A, Hoffmann B, Scarpa F, Kuebler WM, et al. (February 2022).

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Nitzsche B, Rong WW, Goede A, Hoffmann B, Scarpa F, Kuebler WM, et al. (February 2022).

798:; while this is somewhat controversial, it seems that cell signals are transmitted mostly by 249:

As sprouts extend toward the source of the angiogenic stimulus, endothelial cells migrate in

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Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, et al. (October 2004).

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profiles, and their simultaneous or sequential presentation with other appropriate factors.

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Tumors induce blood vessel growth (angiogenesis) by secreting various growth factors (e.g.

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Rust R, Weber RZ, Grönnert L, Mulders G, Maurer MA, Hofer AS, et al. (December 2019).

2031:"Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke" 724:

Besides FGF-1, one of the most important functions of fibroblast growth factor-2 (FGF-2 or

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Cancer cells are cells that have lost their ability to divide in a controlled fashion. A

991:, VEGF; and cell-based therapies, which involve the implantation of specific cell types. 286:, is the formation of a new blood vessel by splitting an existing blood vessel into two. 4002: 3606:"Spatiotemporal control over growth factor signaling for therapeutic neovascularization" 3513: 3473: 3448: 3197: 3161: 3134: 3019: 2976: 2925: 2716:"Dll4 activation of Notch signaling reduces tumor vascularity and inhibits tumor growth" 2676: 2621: 2105: 2046: 1734:"Intussusceptive angiogenesis: its emergence, its characteristics, and its significance" 1466: 1332: 1307: 4337: 4333: 4329: 4283: 4215: 3991: 3954: 3630: 3605: 3581: 3556: 3532: 3497: 3424: 3397: 3263: 3228: 3027: 2889: 2864: 2791: 2764: 2740: 2715: 2640: 2605: 2124: 2089: 2065: 2030: 2029:

Rust R, Grönnert L, Gantner C, Enzler A, Mulders G, Weber RZ, et al. (July 2019).

2006: 1979: 1807: 1782: 1709: 1684: 1430: 1405: 1381: 1356: 1235: 1148: 996: 811: 551: 540: 529: 313: 109: 31: 3893:

Angiogenesis - The Virtual Library of Biochemistry, Molecular Biology and Cell Biology

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Regulates endothelial cell migration and proliferation. Alters vascular permeability.

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are highly regulated during the vessel formation process because destruction of the

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Angiogenesis is a normal and vital process in growth and development, as well as in

69: 4195: 3498:"The clinical impact of mean vessel size and solidity in breast carcinoma patients" 2949: 2700: 2590: 2547: 2346:

Ding YH, Luan XD, Li J, Rafols JA, Guthinkonda M, Diaz FG, Ding Y (December 2004).

1073: 976: 512: 381: 377: 171:. The essential role of angiogenesis in tumor growth was first proposed in 1971 by 105: 3670: 3338: 3321: 2849: 2781: 1355:

Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (July 2014).

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to allow endothelial cells to escape from the original (parent) vessel walls. The

3522: 3449:"Vessel size as a marker of survival in estrogen receptor positive breast cancer" 3374: 3287: 2731: 1700: 1571: 2496: 1607: 1094: 1057: 1000: 839: 831: 757: 575: 334: 298: 262: 235: 125: 120:, vessel elongation and vessel cooption also play a role. Vasculogenesis is the 3892: 3621: 3572: 3464: 3205: 2610:

Proceedings of the National Academy of Sciences of the United States of America

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Proceedings of the National Academy of Sciences of the United States of America

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Ferrara N, Kerbel RS (December 2005). "Angiogenesis as a therapeutic target".

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Herzog B, Pellet-Many C, Britton G, Hartzoulakis B, Zachary IC (August 2011).

2531: 1225: 1053: 915: 893: 885: 873: 671: 657: 645: 568: 508: 309: 180: 3006:

Folkman J (September 1996). "Fighting cancer by attacking its blood supply".

2363: 1996: 830:(MMP). MMPs help degrade the proteins that keep the vessel walls solid. This 206:) which is a proangiogenic growth factor. These biological signals activate 3974: 3110: 3093: 2984: 2880: 2630: 2055: 1832:"On coalescent angiogenesis and the remarkable flexibility of blood vessels" 519: 293:

rats. In this type of vessel formation, the capillary wall extends into the

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10.1002/(SICI)1097-4652(199711)173:2<206::AID-JCP22>3.0.CO;2-C

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Lee D, Kim D, Choi YB, Kang K, Sung ES, Ahn JH, et al. (July 2016).

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during exercise. Nitric oxide results in vasodilation of blood vessels.

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are thought to be an ideal target for therapies directed against them.

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Laboratory Investigation; A Journal of Technical Methods and Pathology

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mainly by processes of sprouting and splitting, but processes such as

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Blood vessel formation, when new vessels emerge from existing vessels

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Spill F, Guerrero P, Alarcon T, Maini PK, Byrne HM (February 2015).

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Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (March 1998).

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can interfere with VEGF-mediated angiogenesis since both SEMA3s and

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adhesion, migration, proliferation, survival and the recruitment of

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Nishida N, Yano H, Nishida T, Kamura T, Kojiro M (September 2006).

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do Amaral RJ, Cavanagh B, O'Brien FJ, Kearney CJ (February 2019).

3245: 1308:"Pathological angiogenesis: mechanisms and therapeutic strategies" 1165: 1124: 984: 803: 799: 795: 791: 710: 706: 630: 467: 439: 435: 156: 3292:(first ed.). Boca Raton: Taylor & Francis. p. 347. 1357:"Type-2 pericytes participate in normal and tumoral angiogenesis" 790:

are protein growth factors which act by binding their receptors,

721:(VEGF), which primarily drives the formation of new capillaries. 257:. These sprouts then form loops to become a full-fledged vessel 3969: 3907: 2563:

American Journal of Physiology. Heart and Circulatory Physiology

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American Journal of Physiology. Heart and Circulatory Physiology

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The first report of angiogenesis can be traced back to the book

1128: 1048: 1044: 858: 787: 783: 762: 748: 725: 579: 502: 453: 449: 4006: 3911: 1926:"Endothelial integrins and angiogenesis: not so simple anymore" 979:, targeting genes of interest for amplification or inhibition; 108:

form from pre-existing vessels, formed in the earlier stage of

1024:

Without angiogenesis a tumor cannot grow beyond a limited size

653: 155:. However, it is also a fundamental step in the transition of 2963:

Folkman J, Klagsbrun M (January 1987). "Angiogenic factors".

983:, which primarily manipulates angiogenic growth factors like 363:

role in the formation of neovasculature, such as in a tumor.

935:

Angiogenesis may be a target for combating diseases such as

715:

distinguishes FGF-1 from other pro-angiogenic growth factors

1602:. Cham: Springer International Publishing. pp. 31–52. 1076:

directed at cancer cells, which rapidly mutate and acquire

1195:

A treatise on the blood, inflammation, and gun-shot wounds

814:

when ligand binding causes a dimerization that initiates

3749:(2). Springer Science and Business Media LLC: 255–256. 3698:

Journal of Tissue Engineering and Regenerative Medicine

3557:"Angiogenesis and the heart: therapeutic implications" 850:

would decrease the integrity of the microvasculature.

3229:"Mesoscopic and continuum modelling of angiogenesis" 1181:

been shown to stabilize vascularisation in collagen-

802:; though some papers show physiologic signaling via 4320: 4280: 4260: 4242: 4214: 4186: 4179: 4154: 4088: 4050: 4041: 3888:

Angiogenesis for Heart Disease from Angioplasty.Org

63: 58: 41: 337:without a corresponding increase in the number of 3834:: CS1 maint: DOI inactive as of September 2024 ( 1973: 1971: 1969: 1732:Burri PH, Hlushchuk R, Djonov V (November 2004). 345:with new cells every time a new vessel develops. 1978:Mecollari V, Nieuwenhuis B, Verhaagen J (2014). 1685:"Tip cells: master regulators of tubulogenesis?" 1593: 1591: 1589: 1280:Angiogenesis insights from a systematic overview 3903:NCI Understanding Cancer series on Angiogenesis 3653:Rouwkema J, Khademhosseini A (September 2016). 1455:Annual Review of Cell and Developmental Biology 1361:American Journal of Physiology. Cell Physiology 1273: 1271: 1168:, blood and other retinal fluids leak into the 944:essential functions. Several diseases, such as 104:is the physiological process through which new 97:3D medical animation still showing angiogenesis 4018: 3923: 1301: 1299: 1210:structures in whole tumors in animal models. 876:(SEMA3s) regulate angiogenesis by modulating 826:Another major contributor to angiogenesis is 8: 1883: 1881: 1879: 1877: 1875: 1689:Seminars in Cell & Developmental Biology 1669:https://www.ncbi.nlm.nih.gov/books/NBK53238/ 1453:Risau W, Flamme I (1995). "Vasculogenesis". 1197:published in 1794, where Scottish anatomist 2243: 2241: 2239: 1629: 1627: 112:. Angiogenesis continues the growth of the 4183: 4047: 4025: 4011: 4003: 3930: 3916: 3908: 1678: 1676: 1139:Angiogenesis is generally associated with 914:can be endogenous or come from outside as 47: 3762: 3709: 3629: 3580: 3531: 3521: 3472: 3423: 3413: 3337: 3262: 3244: 3160: 3150: 3109: 2888: 2831: 2790: 2780: 2739: 2639: 2629: 2211: 2174: 2164: 2123: 2113: 2064: 2054: 2005: 1995: 1949: 1847: 1806: 1749: 1708: 1429: 1380: 1331: 597:Determine formation of arteries or veins 3561:Journal of the Royal Society of Medicine 1600:Biomarkers of the Tumor Microenvironment 1019: 705:(FGF) family with its prototype members 611:, releases and activates growth factors 403: 92: 4167:Protein signalling in heart development 3802:. Morgan & Claypool Life Sciences. 3094:"Angiogenic therapy of the human heart" 2250:Expert Opinion on Investigational Drugs 1830:Pezzella F, Kerbel RS (February 2022). 1306:Dudley AC, Griffioen AW (August 2023). 1267: 1102:Angiogenesis for cardiovascular disease 1043:) and proteins. Growth factors such as 964:, the number one cause of death in the 3827: 1922:Perhaps an inhibitor of angiogenesis: 289:Intussusception was first observed in 80: 38: 3555:Hariawala MD, Sellke FW (June 1997). 1930:The Journal of Clinical Investigation 1093:receptors. This induces a release of 53:Angiogenesis following vasculogenesis 7: 3453:Breast Cancer Research and Treatment 3286:Gonzalez-Perez RR, Rueda BR (2013). 931:Angiogenesis as a therapeutic target 3402:Vascular Health and Risk Management 1467:10.1146/annurev.cb.11.110195.000445 328:fibers into the core to provide an 4268:Vascular remodelling in the embryo 3604:Cao L, Mooney DJ (November 2007). 3028:10.1038/scientificamerican0996-150 1984:Frontiers in Cellular Neuroscience 1637:Retinal and Choroidal Angiogenesis 989:vascular endothelial growth factor 741:Vascular endothelial growth factor 719:vascular endothelial growth factor 253:, using adhesion molecules called 25: 3898:Visualizing Angiogenesis with GFP 3808:10.4199/C00017ED1V01Y201009ISP009 2575:10.1152/ajpheart.2000.279.4.H1540 2285:Trends in Cardiovascular Medicine 617:plasminogen activator inhibitor-1 4099:Primary interventricular foramen 3864:10.1016/j.biotechadv.2011.12.001 1683:Weavers H, Skaer H (July 2014). 1560:European Journal of Pharmacology 1088:Formation of tumor blood vessels 1080:to treatment. For this reason, 3233:Journal of Mathematical Biology 2454:10.1152/japplphysiol.01031.2003 2411:10.1152/japplphysiol.00748.2003 2166:10.1186/gb-2001-2-3-reviews3005 1902:10.1152/japplphysiol.00035.2004 304:are reorganized and the vessel 3610:Advanced Drug Delivery Reviews 3186:Journal of Theoretical Biology 2352:Current Neurovascular Research 1490:Journal of Cellular Physiology 1068:and a waste disposal pathway. 999:, inflammatory responses, and 806:as well. These receptors are 730:platelet-derived growth factor 1: 3794:Adair TH, Montani JP (2010). 3671:10.1016/j.tibtech.2016.03.002 3339:10.1158/1078-0432.CCR-04-0378 3289:Tumor angiogenesis regulators 2869:Molecular Biology of the Cell 2833:10.1016/s0092-8674(00)81402-6 2782:10.1080/19420862.2016.1171432 2442:Journal of Applied Physiology 2399:Journal of Applied Physiology 2297:10.1016/S1050-1738(02)00259-1 1890:Journal of Applied Physiology 3523:10.1371/journal.pone.0075954 3375:10.1016/j.molmed.2010.01.004 3363:Trends in Molecular Medicine 3139:Advanced Biomedical Research 2732:10.1182/blood-2007-11-126045 1701:10.1016/j.semcdb.2014.04.009 1572:10.1016/j.ejphar.2023.176176 1176:Tissue engineered constructs 280:Intussusceptive angiogenesis 275:Intussusceptive angiogenesis 269:Intussusceptive angiogenesis 4134:Primary interatrial foramen 3133:Zarei P, Ghasemi F (2024). 3092:Folkman J (February 1998). 2497:10.1152/ajpheart.00743.2002 2149:"Fibroblast growth factors" 1924:Sheppard D (October 2002). 1640:. Springer. pp. 119–. 1608:10.1007/978-3-030-98950-7_3 1231:The Angiogenesis Foundation 981:protein replacement therapy 444:Integrate survival signals 324:. These cells begin laying 163:one, leading to the use of 4415: 3622:10.1016/j.addr.2007.08.012 3573:10.1177/014107689709000604 3465:10.1007/s10549-023-06974-4 3206:10.1016/j.jtbi.2005.12.022 2262:10.1517/13543784.7.12.2011 2147:Ornitz DM, Itoh N (2001). 2115:10.1038/s41598-019-56634-1 1849:10.1007/s10456-021-09825-2 1799:10.1007/s10456-021-09824-3 1422:10.1007/s10456-021-09824-3 1373:10.1152/ajpcell.00084.2014 1324:10.1007/s10456-023-09876-7 1282:. New York: Nova Science. 903: 810:. Thus, they can initiate 694: 621:stabilizes nearby vessels 352: 272: 132:cell precursors, and from 29: 3945: 3755:10.1007/s10456-016-9496-7 3415:10.2147/vhrm.2006.2.3.213 3255:10.1007/s00285-014-0771-1 2532:10.1007/s00441-003-0749-6 1634:Penn JS (11 March 2008). 1251:Proteases in angiogenesis 863:notch family of receptors 159:from a benign state to a 75: 46: 3398:"Angiogenesis in cancer" 3326:Clinical Cancer Research 2520:Cell and Tissue Research 2364:10.2174/1567202043361875 1997:10.3389/fncel.2014.00328 1278:Santulli G, ed. (2013). 828:matrix metalloproteinase 703:fibroblast growth factor 697:Fibroblast growth factor 151:and in the formation of 30:Not to be confused with 4229:Posterior cardinal vein 4162:Aorticopulmonary septum 3810:(inactive 2024-09-12). 3659:Trends in Biotechnology 3111:10.1161/01.CIR.97.7.628 2985:10.1126/science.2432664 2881:10.1091/mbc.E09-12-1061 2631:10.1073/pnas.0611206104 2056:10.1073/pnas.1905309116 1062:circulating tumor cells 962:cardiovascular diseases 946:ischemic chronic wounds 926:Application in medicine 360:Coalescent angiogenesis 355:Coalescent angiogenesis 349:Coalescent angiogenesis 165:angiogenesis inhibitors 118:coalescent angiogenesis 4224:Anterior cardinal vein 4114:Atrioventricular canal 3852:Biotechnology Advances 3152:10.4103/abr.abr_170_23 1738:Developmental Dynamics 1025: 912:angiogenesis inhibitor 906:Angiogenesis inhibitor 662:Regulates endothelial 603:plasminogen activators 372:Mechanical stimulation 284:splitting angiogenesis 192:Sprouting angiogenesis 98: 77:Anatomical terminology 4234:Common cardinal veins 1023: 695:Further information: 565:matrix macromolecules 430:Affects permeability 238:into the surrounding 96: 4104:Endocardial cushions 1256:Vasculogenic mimicry 1162:macular degeneration 1156:Macular degeneration 950:macular degeneration 848:extracellular matrix 664:transdifferentiation 609:extracellular matrix 586:junctional molecules 495:extracellular matrix 388:Chemical stimulation 330:extracellular matrix 183:are characteristic. 167:in the treatment of 4070:Primitive ventricle 4033:Development of the 3514:2013PLoSO...875954M 3198:2006JThBi.241..564M 3020:1996SciAm.275c.150F 3008:Scientific American 2977:1987Sci...235..442F 2934:10.1038/nature04483 2926:2005Natur.438..967F 2685:10.1038/nature05571 2677:2007Natur.445..776H 2622:2007PNAS..104.3219L 2106:2019NatSR...920040R 2047:2019PNAS..11614270R 2041:(28): 14270–14279. 1006:Alzheimer's disease 973:mechanism of action 900:Chemical inhibition 874:Class 3 semaphorins 869:Class 3 semaphorins 859:Delta-like ligand 4 474:smooth muscle cells 466:(BB-homodimer) and 218:, begin to release 4378:Vitelline arteries 4342:Inferior vena cava 4109:Septum intermedium 4060:Truncus arteriosus 4035:circulatory system 3960:Granulation tissue 3063:10.1007/PL00001972 2569:(4): H1540–H1547. 2491:(5): H1668–H1678. 2386:on April 19, 2012. 2159:(3): REVIEWS3005. 2094:Scientific Reports 1751:10.1002/dvdy.20184 1145:endurance exercise 1026: 1016:Tumor angiogenesis 818:on key tyrosines. 458:Stabilize vessels 153:granulation tissue 134:neovascularization 99: 4386: 4385: 4354:Ductus arteriosus 4322:Fetal circulation 4276: 4275: 4175: 4174: 4095:Atrioventricular 4089:Chamber formation 4000: 3999: 3711:10.1002/term.2789 3616:(13): 1340–1350. 3332:(20): 6897–6904. 3299:978-1-4665-8097-8 3145:(15): 9759–9815. 2971:(4787): 442–447. 2920:(7070): 967–974. 2875:(15): 2766–2776. 2671:(7129): 776–780. 2256:(12): 2011–2015. 2222:10.1021/bi9521755 1647:978-1-4020-6779-2 1617:978-3-030-98950-7 1566:(15): 9759–9815. 1289:978-1-62618-114-4 1246:Neuroangiogenesis 1183:glycosaminoglycan 1082:endothelial cells 1058:endothelial cells 920:dietary component 836:endothelial cells 709:(acidic FGF) and 688: 687: 339:endothelial cells 232:endothelial cells 228:basement membrane 226:that degrade the 212:endothelial cells 91: 90: 86: 16:(Redirected from 4406: 4362:Umbilical artery 4350:Pulmonary artery 4302:Connecting stalk 4184: 4129:Foramen secundum 4075:Primitive atrium 4048: 4027: 4020: 4013: 4004: 3932: 3925: 3918: 3909: 3876: 3875: 3846: 3840: 3839: 3833: 3825: 3823: 3822: 3791: 3785: 3784: 3766: 3738: 3732: 3731: 3713: 3689: 3683: 3682: 3650: 3644: 3643: 3633: 3601: 3595: 3594: 3584: 3552: 3546: 3545: 3535: 3525: 3493: 3487: 3486: 3476: 3444: 3438: 3437: 3427: 3417: 3393: 3387: 3386: 3358: 3352: 3351: 3341: 3317: 3311: 3310: 3308: 3306: 3283: 3277: 3276: 3266: 3248: 3224: 3218: 3217: 3181: 3175: 3174: 3164: 3154: 3130: 3124: 3123: 3113: 3089: 3083: 3082: 3046: 3040: 3039: 3003: 2997: 2996: 2960: 2954: 2953: 2909: 2903: 2902: 2892: 2860: 2854: 2853: 2835: 2811: 2805: 2804: 2794: 2784: 2760: 2754: 2753: 2743: 2711: 2705: 2704: 2660: 2654: 2653: 2643: 2633: 2616:(9): 3219–3224. 2601: 2595: 2594: 2558: 2552: 2551: 2515: 2509: 2508: 2480: 2474: 2473: 2448:(4): 1445–1450. 2437: 2431: 2430: 2394: 2388: 2387: 2382:. Archived from 2343: 2337: 2336: 2315: 2309: 2308: 2280: 2274: 2273: 2245: 2234: 2233: 2215: 2206:(7): 2086–2094. 2195: 2189: 2188: 2178: 2168: 2144: 2138: 2137: 2127: 2117: 2085: 2079: 2078: 2068: 2058: 2026: 2020: 2019: 2009: 1999: 1975: 1964: 1963: 1953: 1942:10.1172/JCI16713 1920: 1914: 1913: 1896:(3): 1119–1128. 1885: 1870: 1869: 1851: 1827: 1821: 1820: 1810: 1778: 1772: 1771: 1753: 1729: 1723: 1722: 1712: 1680: 1671: 1665: 1659: 1658: 1656: 1654: 1631: 1622: 1621: 1595: 1584: 1583: 1555: 1549: 1548: 1545:10.1002/cem.3545 1528: 1522: 1521: 1485: 1479: 1478: 1450: 1444: 1443: 1433: 1401: 1395: 1394: 1384: 1352: 1346: 1345: 1335: 1303: 1294: 1293: 1275: 1221:Aerobic exercise 1141:aerobic exercise 878:endothelial cell 808:tyrosine kinases 648:differentiation 404: 396:e.g. VEGF, FGF. 343:microvasculature 282:, also known as 144:and in disease. 83:edit on Wikidata 51: 39: 21: 4414: 4413: 4409: 4408: 4407: 4405: 4404: 4403: 4389: 4388: 4387: 4382: 4373:Vitelline veins 4316: 4284:hemangiogenesis 4282: 4272: 4256: 4238: 4210: 4171: 4150: 4139:Septum secundum 4084: 4037: 4031: 4001: 3996: 3985:Intussusception 3941: 3936: 3884: 3879: 3848: 3847: 3843: 3826: 3820: 3818: 3793: 3792: 3788: 3740: 3739: 3735: 3691: 3690: 3686: 3652: 3651: 3647: 3603: 3602: 3598: 3554: 3553: 3549: 3495: 3494: 3490: 3446: 3445: 3441: 3395: 3394: 3390: 3360: 3359: 3355: 3319: 3318: 3314: 3304: 3302: 3300: 3285: 3284: 3280: 3226: 3225: 3221: 3183: 3182: 3178: 3132: 3131: 3127: 3091: 3090: 3086: 3048: 3047: 3043: 3005: 3004: 3000: 2962: 2961: 2957: 2911: 2910: 2906: 2862: 2861: 2857: 2813: 2812: 2808: 2762: 2761: 2757: 2713: 2712: 2708: 2662: 2661: 2657: 2603: 2602: 2598: 2560: 2559: 2555: 2517: 2516: 2512: 2482: 2481: 2477: 2439: 2438: 2434: 2396: 2395: 2391: 2345: 2344: 2340: 2317: 2316: 2312: 2282: 2281: 2277: 2247: 2246: 2237: 2213:10.1.1.660.7607 2197: 2196: 2192: 2146: 2145: 2141: 2087: 2086: 2082: 2028: 2027: 2023: 1977: 1976: 1967: 1923: 1921: 1917: 1887: 1886: 1873: 1829: 1828: 1824: 1780: 1779: 1775: 1731: 1730: 1726: 1682: 1681: 1674: 1666: 1662: 1652: 1650: 1648: 1633: 1632: 1625: 1618: 1597: 1596: 1587: 1557: 1556: 1552: 1530: 1529: 1525: 1487: 1486: 1482: 1452: 1451: 1447: 1403: 1402: 1398: 1354: 1353: 1349: 1305: 1304: 1297: 1290: 1277: 1276: 1269: 1265: 1260: 1216: 1207: 1191: 1178: 1158: 1137: 1109:neoangiogenesis 1104: 1090: 1078:drug resistance 1030:malignant tumor 1018: 933: 928: 908: 902: 884:. Furthermore, 871: 856: 824: 816:phosphorylation 772: 738: 699: 693: 559: 555: 548: 544: 537: 533: 489:TGF-β receptors 402: 390: 374: 369: 357: 351: 277: 271: 194: 189: 87: 54: 35: 28: 23: 22: 18:Vascularisation 15: 12: 11: 5: 4412: 4410: 4402: 4401: 4391: 4390: 4384: 4383: 4381: 4380: 4375: 4365: 4364: 4338:Ductus venosus 4334:Umbilical vein 4330:umbilical cord 4326: 4324: 4318: 4317: 4315: 4314: 4309: 4304: 4299: 4294: 4288: 4286: 4281:Extraembryonic 4278: 4277: 4274: 4273: 4271: 4270: 4264: 4262: 4258: 4257: 4255: 4254: 4248: 4246: 4240: 4239: 4237: 4236: 4231: 4226: 4220: 4218: 4212: 4211: 4209: 4208: 4203: 4198: 4192: 4190: 4181: 4177: 4176: 4173: 4172: 4170: 4169: 4164: 4158: 4156: 4152: 4151: 4149: 4148: 4147: 4146: 4141: 4136: 4131: 4126: 4118: 4117: 4116: 4111: 4106: 4101: 4092: 4090: 4086: 4085: 4083: 4082: 4077: 4072: 4067: 4062: 4056: 4054: 4045: 4039: 4038: 4032: 4030: 4029: 4022: 4015: 4007: 3998: 3997: 3995: 3994: 3992:Vasculogenesis 3989: 3988: 3987: 3977: 3972: 3967: 3962: 3957: 3955:Maggot therapy 3952: 3946: 3943: 3942: 3937: 3935: 3934: 3927: 3920: 3912: 3906: 3905: 3900: 3895: 3890: 3883: 3882:External links 3880: 3878: 3877: 3858:(3): 396–401. 3841: 3786: 3733: 3704:(2): 261–273. 3684: 3665:(9): 733–745. 3645: 3596: 3567:(6): 307–311. 3547: 3508:(10): e75954. 3488: 3459:(2): 293–304. 3439: 3408:(3): 213–219. 3388: 3369:(3): 122–132. 3353: 3312: 3298: 3278: 3239:(3): 485–532. 3219: 3192:(3): 564–589. 3176: 3125: 3104:(7): 628–629. 3084: 3057:(6): 589–599. 3041: 3014:(3): 150–154. 2998: 2955: 2904: 2855: 2826:(6): 735–745. 2806: 2775:(5): 892–904. 2755: 2726:(5): 1904–11. 2706: 2655: 2596: 2553: 2510: 2475: 2432: 2389: 2358:(5): 411–420. 2338: 2327:(5): 508–517. 2310: 2291:(3): 116–122. 2275: 2235: 2190: 2153:Genome Biology 2139: 2080: 2021: 1965: 1936:(7): 913–914. 1915: 1871: 1822: 1773: 1744:(3): 474–488. 1724: 1695:(100): 91–99. 1672: 1660: 1646: 1623: 1616: 1585: 1550: 1523: 1496:(2): 206–210. 1480: 1445: 1396: 1367:(1): C25–C38. 1347: 1318:(3): 313–347. 1295: 1288: 1266: 1264: 1261: 1259: 1258: 1253: 1248: 1243: 1238: 1236:Arteriogenesis 1233: 1228: 1223: 1217: 1215: 1212: 1206: 1205:Quantification 1203: 1190: 1187: 1177: 1174: 1157: 1154: 1149:arteriogenesis 1136: 1133: 1103: 1100: 1089: 1086: 1017: 1014: 997:immunogenicity 971:Regarding the 932: 929: 927: 924: 904:Main article: 901: 898: 870: 867: 855: 852: 823: 820: 812:cell signaling 771: 768: 737: 734: 692: 689: 686: 685: 682: 678: 677: 674: 667: 666: 660: 650: 649: 642: 636: 635: 633: 623: 622: 619: 613: 612: 605: 599: 598: 595: 589: 588: 582: 572: 571: 561: 557: 553: 546: 542: 535: 531: 525: 524: 522: 516: 515: 505: 499: 498: 491: 477: 476: 470: 460: 459: 456: 446: 445: 442: 432: 431: 428: 422: 421: 418: 412: 411: 408: 401: 398: 394:growth factors 389: 386: 373: 370: 368: 365: 353:Main article: 350: 347: 322:myofibroblasts 314:growth factors 302:cell junctions 273:Main article: 270: 267: 193: 190: 188: 185: 110:vasculogenesis 89: 88: 79: 73: 72: 67: 61: 60: 56: 55: 52: 44: 43: 32:vasculogenesis 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 4411: 4400: 4397: 4396: 4394: 4379: 4376: 4374: 4370: 4367: 4366: 4363: 4359: 4355: 4351: 4347: 4343: 4339: 4335: 4331: 4328: 4327: 4325: 4323: 4319: 4313: 4310: 4308: 4305: 4303: 4300: 4298: 4295: 4293: 4292:Blood islands 4290: 4289: 4287: 4285: 4279: 4269: 4266: 4265: 4263: 4259: 4253: 4250: 4249: 4247: 4245: 4244:Lymph vessels 4241: 4235: 4232: 4230: 4227: 4225: 4222: 4221: 4219: 4217: 4213: 4207: 4204: 4202: 4201:Aortic arches 4199: 4197: 4194: 4193: 4191: 4189: 4185: 4182: 4178: 4168: 4165: 4163: 4160: 4159: 4157: 4153: 4145: 4144:Foramen ovale 4142: 4140: 4137: 4135: 4132: 4130: 4127: 4125: 4124:Septum primum 4122: 4121: 4119: 4115: 4112: 4110: 4107: 4105: 4102: 4100: 4097: 4096: 4094: 4093: 4091: 4087: 4081: 4080:Sinus venosus 4078: 4076: 4073: 4071: 4068: 4066: 4065:Bulbus cordis 4063: 4061: 4058: 4057: 4055: 4053: 4052:Tubular heart 4049: 4046: 4044: 4040: 4036: 4028: 4023: 4021: 4016: 4014: 4009: 4008: 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