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Encyclopedia > Angiogenesis

Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over this, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel formation by splitting of existing ones. The arterial system The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... Vasculogenesis is the process of blood vessel formation occuring by a de novo production of endothelial cells. ... Intussusception is the process whereby a new blood vessel is created by the splitting of an existing blood vessel in two. ...


Angiogenesis is a normal process in growth and development, as well as in wound healing. However, this is also a fundamental step in the transition of tumors from a dormant state to a malignant state. Tumor (American English) or tumour (British English) originally means swelling, and is sometimes still used with that meaning. ... In medicine, malignant is a clinical term that is used to describe a clinical course that progresses rapidly to death. ...

Contents


Types of Angiogenesis

Sprouting Angiogenesis

Sprouting angiogenesis was originally the only known form of angiogenesis. It is very simple and occurs in several stages. First, the basement membrane degrades to allow endothelial cells to escape from the vessel walls. The endothelial cells then proliferate into the surrounding matrix and form solid sprouts connecting neighboring vessels. These sprouts then become a full-fledged vessel lumen as cells migrate to the site of angiogenesis. Sprouting is slow as it is reliant on cell proliferation but is able to spread new vessels across gaps in the vasculature. It is markedly different from splitting angiogenesis, however, because it forms entirely new vessels as opposed to splitting existing vessels (Burri, Hlushchuk, & Djonov, 2004). The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ...


Intussusceptive Angiogenesis

Please see intussusception. Intussusception is the process whereby a new blood vessel is created by the splitting of an existing blood vessel in two. ...


Therapeutic angiogenesis

The application of specific compounds which may inhibit or induce the creation of new blood vessels in the body in order to ameriolate disease. 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 retard repair or some other function. Several diseases (eg age-related macular degeneration, ischemic chronic wounds) are the result of failure or insufficient blood vessel formation. These diseases may be treated by a local expansion of blood vessels, thus bringing new nutrients to the site facilitating repair.


Mechanical Stimulation

Mechanical stimulation of angiogenesis is not well characterized. There is a significant amount of controversy with regard to shear stress acting on capillaries to cause angiogenesis, although current knowledge suggests that increased muscle contractions may increase angiogenesis (Prior et al., 2004).


Chemical Stimulation

VEGF

Chemically, VEGF is well understood to be a major contributor to increasing the number of capillaries in a given network. Initial in vitro studies demonstrated that bovine capillary endothelial cells will proliferate and show signs of tube structures upon stimulation by VEGF and bFGF, although the results were more pronounced with VEGF (Goto, Goto, Weindel, & Folkman, 1993). 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 (Ding et al., 2004; Gavin et al., 2004; Kraus, Stallings, Yeager, & Gavin, 2004; Lloyd, Prior, Yang, & Terjung, 2003). In vitro 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 (Prior et al., 2004). Vascular endothelial growth factor or VEGF is an important signal protein involved in angiogenesis. ... Member of the Fibroblast Growth Factor familly. ...


VEGF causes a massive signaling cascade in endothelial 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, producting NO), proliferation/survival (bFGF), migration (ICAMs/VCAMs/MMPs) and finally differentiation into mature blood 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 mRNA production of VEGF receptors 1 and 2. The increase in receptor production means that 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 because inhibition of NO significantly reduces the effects of angiogenic growth factors. However, inhibition of NO during exercise does not inhibit angiogenesis indicating that there are other factors involved in the angiogenic response (Prior et al., 2004). Vascular endothelial growth factor or VEGF is an important signal protein involved in angiogenesis. ... The interaction of mRNA in a eukaryote cell. ...


MMP

Another major contributor to angiogenesis is matrix metalloproteinase (MMP). MMPs help degrade the proteins that keep the vessel walls solid. This proteolysis allows the endothelial cells to escape into the interstitial matrix as seen in sprouting angiogenesis. Inhibition of MMPs prevents the formation of new capillaries (Haas et al., 2000). These enzymes are highly regulated during the vessel formation process because wanton destruction of the extracellular matrix would destroy the integrity of the microvasculature (Prior et al., 2004). MMP may stand for: Mixed Member Proportional electoral system. ... MMP may stand for: Mixed Member Proportional electoral system. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... MMP may stand for: Mixed Member Proportional electoral system. ... The word capillary is used to describe any very narrow tube or channel through which a fluid can pass. ... Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ... In biology, extracellular matrix (ECM) is any material part of a tissue that is not part of any cell. ...


Applications of Angiogenesis

Tumor angiogenesis

Cancer cells are cells that have lost control of their ability to divide in a controlled fashion. A tumor consists of a population of rapidly dividing and growing cancer cells. Mutations rapidly accrue within the population. These mutations (variation) allow the cancer cells (or sub-populations of cancer cells within a tumor) to develop drug resistance and escape therapy. Tumors cannot grow beyond a certain size, generally 1-2 mm3, due to a lack of oxygen and other essential nutrients. When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... It has been suggested that extracellular be merged into this article or section. ... In biology, mutations are changes to the genetic material (usually DNA or RNA). ... Organisms are said to be drug-resistant when they are no longer affected by drugs that are meant to neutralize them. ... Look up Therapy in Wiktionary, the free dictionary Therapy (in Greek: θεραπεία) or treatment is the attempted remediation of a health problem, usually following a diagnosis. ...


Tumors induce blood vessel growth (angiogenesis) by secreting various growth factors (e.g. Vascular Endothelial Growth Factor or VEGF). Growth factors, such as bFGF and VEGF can induce capillary growth into the tumor, supplying required nutrients and allowing for tumor expansion. Thus angiogenesis is a necessary and required step for transition from a small harmless cluster of cells, to a large tumor. Angiogenesis is also required for the spread of a tumor, or metastasis. 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 that the blood vessel in a given solid tumor may in fact be mosaic vessels, comprised of endothelial cells and tumor cells. This mosaicity allows for substantial shedding of tumor cells into the vasculature. The subsequent growth of such metastases will also require a supply of nutrients and oxygen. Vascular endothelial growth factor or VEGF is an important signal protein involved in angiogenesis. ... Member of the Fibroblast Growth Factor familly. ... Metastasis (Greek: change of the state) is the spread of cancer from its primary site to other places in the body. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless Atomic mass 15. ...


Endothelial cells are much more genomically stable than cancer cells, and have a doubling time of approximately 120 days. The genomic stability allied to their longevity (compared to the tumor cell) makes then an ideal target for therapies directed against them. They will not 'escape' therapy, as they will not undergo mitosis at such a rapid rate and carry any drug resistance variation through to the next generation within the lifespan of the therapy. Light micrograph of a newt kidney cell in early anaphase of mitosis. ...


Angiogenesis research is a cutting edge field in cancer research, and recent evidence also suggests that traditional therapies, such as radiation therapy, may actually work in part by targeting the genomically stable endothelial cell compartment, rather than the genomicaly unstable tumor cell compartment. In short, the therapy is the selection agent which is being used to kill a cell compartment. Tumor cells evolve resistance rapidly due to rapid generation time (days) and genomic instability (variation), whereas endothelial cells are a good target because of a long generation time (months) and genomic stability (low variation). Cancer research is the intense scientific effort to understand the development of cancer and identify potential therapies. ...


This is an example of selection in action at the cellular level, using a selection pressure to target and differentiate between varying populations of cells. The end result is the extinction of one species or population of cells (endothelial cells), followed by the collapse of the ecosystem (the tumor). Selection is hierachically classified into natural and artificial selection. ... In biology and ecology, extinction is the ceasing of existence of a species or group of taxa. ... In ecology, an ecosystem is a combination of all the living and non-living elements of an area. ...


Angiogenesis-based tumour therapy relies on natural and synthetic angiogenesis inhibitors like angiostatin, endostatin and tumstatin. These are proteins that mainly originate as specific fragments pre-existing structural proteins like collagen or plasminogen. Dr. Judah Folkman was the first to identify stopping angiogenesis as a strategy for attacking cancerous tumors. A drug that inhibits angiogenesis. ... Angiostatin is a natural angiogenesis inhibitor that is currently underlying clinical trials for its use in anticancer therapy. ... An endostatin is a naturally-occurring chemical in the human body that serves as an anti-angiogenesis agent. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Tropocollagen triple helix. ... Plasmin is an important degrading enzyme (EC 3. ... Dr. Judah Folkman (b. ...


Recently the 1st FDA approved therapy targeted at angiogenesis in cancer came on the market in the US. This is a monoclonal antibody directed against an isoform of VEGF. The commercial name of this antibody is Avastin, and the therapy has been approved for use in colorectal cancer in combination with established chemotherapy. Bevacizumab is an anti-angiogenesis drug used in treatment of cancer. ...


Exercise

Angiogenesis is generally associated with aerobic exercise and endurance exercise. While arteriogenesis 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 capillaries allows the network to delivery 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 exists to suggest that increased capillarity is required in endurance exercise to increase the maximum oxygen delivery (Prior et al., 2004). In physical exercise, Aerobic exercise is complementary to anaerobic exercise. ... Arteriogenesis refers to an increase in the diameter of existing arterial vessels. ...


Macular Degeneration

Overexpression of VEGF causes increased permeability in blood vessels in addition to stimulating angiogenesis. In wet macular degeneration VEGF causes proliferation of capillaries into the retina. Since the increase in angiogenesis also causes edema, blood and other retinal fluids leak into the retina causing loss of vision. A novel treatment of this disease is to use a VEGF inhibiting aptamer to stop the main signaling cascade for angiogenesis. Listen to this article · (info) This audio file was created from an article revision dated 2005-07-19, and does not reflect subsequent edits to the article. ... Edema (BE: oedema, formerly known as dropsy) is swelling of any organ or tissue due to accumulation of excess fluid. ... Aptamers are oligo nucliec acid or peptide molecules selected from large randome sequence pool to bind to specific target molecule. ...


See also

Arteriogenesis refers to an increase in the diameter of existing arterial vessels. ... In physical exercise, Aerobic exercise is complementary to anaerobic exercise. ...

References

  1. Burri, P. H., Hlushchuk, R., & Djonov, V. Intussusceptive angiogenesis: Its emergence, its characteristics, and its significance. Devel Dynam 231: 474-488, 2004.
  2. Ding, Y. H., Luan, X. D., Li, J., Rafols, J. A., Guthinkonda, M., & Diaz, F. G. et al. Exercise-induced overexpression of angiogenic factors and reduction of ischemia/reperfusion injury in stroke. Curr Neurovasc Res 1: 411-20, 2004.
  3. Djonov, V., Baum, O., & Burri, P. H. Vascular remodeling by intussusceptive angiogenesis. Cell Tissue Res 314: 107–117, 2003.
  4. Gavin, T. P., Robinson, C. B., Yeager, R. C., England, J. A., Nifong, L. W., & Hickner, R. C. Angiogenic growth factor response to acute systemic exercise in human skeletal muscle. J App Physiol 96: 19-24, 2004.
  5. Goto, F., Goto, K., Weindel, K., & Folkman, J. 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. Lab Inves 69: 508-17, 1993.
  6. Haas, T. L., Milkiewicz, M., Davis, S. J., Zhou, A. L., Egginton, S., Brown, M. D., Madri, J. A., Hudlicka, O. Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am J Physiol Heart Circ Physiol 279: H1540-H1547, 2000.
  7. Kraus, R. M., Stallings, H. W., Yeager, R. C., & Gavin, T. P. Circulating plasma VEGF response to exercise in sedentary and endurance-trained men. J App Physiol 96: 1445-50, 2004.
  8. Lloyd, P. G., Prior, B. M., Yang, H. T., & Terjung, R. L. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. Am J Physiol Heart Circ Physiol 284: 1668-78, 2003.
  9. Prior, B. M., Yang, H. T., & Terjung, R. L. What makes vessels grow with exercise training? J App Physiol 97: 1119-28, 2004.

External links


  Results from FactBites:
 
angiogenesis - definition of angiogenesis in Encyclopedia (555 words)
Angiogenesis is the physiological process involving the formation of new blood vessels from pre-existing vessels.
Angiogenesis is also required for the spread of a tumor, or metastasis.
Angiogenesis research is a cutting edge field in cancer research, and recent evidence also suggests that traditional therapies, such as radiation therapy, may actually work in part by targeting the genomically stable endothelial cell compartment, rather than the genomicaly unstable tumor cell compartment.
:: Science :: Biology :: Physiology :: Angiogenesis (430 words)
Angioworld.com - Angiogenesis and the new approach to treatment of angiodependent deseases (cancers, arthritis, psoriasis) based on antiangiogenic activity of CartCell.
Angiogenesis Center - Information on angiogenesis and several methods of treatment of cardiovascular disease are linked.
Angiogenesis Research Center - New treatments for interventional cardiology are studied at this Harvard facility.
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