The strategies currently used to halt the development and progression of
atherosclerosis and the restenotic neointimal lesions are suboptimal. Understanding
the mechanisms of angiogenic growth within the neointima of atherosclerotic
and restenotic lesions may lead to the development of new therapies designed to
halt the progression of atherosclerosis and inhibit restenosis after percutaneous
coronary intervention. Intra-plaque hemorrhage as a result of premature neointimal
vasa vasorum represents a critical event in the induction of instability in
atherosclerotic coronary lesions. The removal of abnormal neovascularization by
molecular therapies may interfere with intra-plaque hemorrhage and hence may
halt the progression of atherosclerosis. The growth factors, the angiogenic
enzymes, the chemokines, the endothelial specific receptors, and the adhesion
molecules, which are involved in the expansion of vasa vasorum, constitute
potential targets for such therapies. The vascular endothelial growth factor (VEGF)
has an important role in the induction and the maintenance of new blood vessel
formation. Thus, the local administration of soluble VEGF receptor, anti-VEGF
antibodies, or antibodies that bind to the VEGF receptor, will block VEGF binding
to its receptors and thereby block its angiogenic effects. Either stent- or catheterbased
therapy may be a viable treatment option for delivering drugs, such as the
VEGF-specific antibody (bevacizumab). By inhibiting intralesion angiogenesis,
and thus the thickening of neointima, by catheter-based therapy, we may halt the
development of high risk unstable plaques and restenosis after coronary
interventions. In addition, a combined therapeutic approach with balloon-based
strategies with antiangiogenic, antithrombotic, and prohealing agents, and with
stents targeting plaques at multiple steps would be more effective.
Keywords: Antiangiogenesis, artherosclerosis, coronary artery disease, coronary
intervention.
