Plaque Angiogenesis: Its Functions and Regulation

Therapeutic "angiogenesis" trials refer to the stimulation of collateral arterioles or larger-caliber blood vesselsthat perfuse ischemic myocardium and tissues caused byimpaired blood flow in occluded or stenotic native arteries. Angiogenesis, or the formation of small-caliber capillary-like blood vessels, occurs within the atheroscleroticlesions that are responsible for the vascular occlusionsthemselves. Plaque neovascularization comprises a network of capillaries that arise from the adventitial vasa vasorum and extend into the thickened intimal layer associated with atherosclerosis and other conditions of vascularinjury and inflammation. These plaque capillaries areconduits for the exchange of inflammatory cells inatherosclerotic lesions and therefore may affect theirgrowth rate or susceptibility to rupture. Thus, the development of agents that are either positive or negative regulators of arteriogenesis and angiogenesis may have dualtherapeutic applications in cardiovascular diseases—toameliorate impaired tissue perfusion in the setting of established flow-limiting vascular stenosis, or to delay theprogression of atherosclerotic lesions that cause ischemia, thereby obviating the need for collaterals. Although strategies to promote arteriogenesis have advanced into clinical investigations, this paper focuses onthe functions and potential regulators of plaque angiogenesis in atherosclerosis...