Biomedical Engineering Reference
In-Depth Information
Pro-Angiogenic
Factors:
VEGF
FGF
PDGF
Angiopoietin
Optimal
Angiogenesis
Anti-Angiogenic
Factors:
Angiostatin
Endostatin
Fig. 3
Endogenous pro-angiogenic and anti-angiogenic factors
thereby inhibiting endothelial cell growth, migration, and proliferation. Endostatin
inhibits capillary endothelial cell proliferation. Both angiostatin and endostatin are
potent suppressors of tumor growth and metastasis [
22
,
23
]. For instance, angio-
statin blocks angiogenesis induced by Kaposi's sarcoma cells; Kaposi's sarcoma is a
highly angiogenic and inflammation-associated tumor [
24
]. Retinoids are another
important class of molecules which oppose angiogenesis. Retinoids decrease VEGF
expression in skin keratinocytes, and inhibit cell proliferation and differentiation
[
25
]; retinoids are well-known teratogens due to their anti-angiogenic activity.
Natural corticosteroids such as tetrahydrocortisol are also powerful inhibitors of
angiogenesis [
26
].
Ultimately, the cocktail of pro-angiogenic and anti-angiogenic factors in a given
tissue site determines whether blood vessel formation will take place (Fig.
3
).
Pro-angiogenic mediators such as VEGF and FGF, as well as anti-angiogenic
mediators such as angiostatin and endostatin, are all potential targets for angiogen-
esis-modulating therapies. Both pro-angiogenic and anti-angiogenic pathways may
be exploited to either encourage angiogenesis to treat injured and ischemic tissues, or
discourage angiogenesis to treat cancerous tumors and inflammatory diseases. The
next section will describe a prototypical pro-angiogenic approach: therapeutic
angiogenesis for healing the heart.
3 Therapeutic Angiogenesis for Coronary Artery Disease
Coronary artery disease is the leading killer of men and women worldwide; it has
been projected that deaths due to cardiovascular diseases will rise to 23.3 million per
year by 2030 [
27
]. Congestive heart failure, the end stage of many heart diseases,
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