Plaque Angiogenesis Versus Compensatory Arteriogenesis in Atherosclerosis

any atherosclerotic lesions are vascularized by a network of capillaries that arise from the adventitial vasa vasorum. 1 These capillaries may be important regulators of plaque instability.Reflecting their inflammatory microenvironment, the capillaries are immature endothelial tubes with disorganized branching, fragile and prone to rupture.The accumulation of erythrocytes after intraplaque hemorrhage may promote the transition from lesion stability to instability. 2 Research interest in both angiogenesis and arteriogenesis, the maturation or de novo growth of collateral vessels, 3,4 in atherosclerotic disease has intensified in recent years, reflecting the emerging success of antiangiogenesis strategies in cancer therapy.The bench-to-bedside milepost was reached in February 2004, when the US Food and Drug Administration approved bevacizumab (Avastin, Genentech), an antivascular endothelial growth factor (VEGF) monoclonal antibody, for the treatment of colorectal cancer.5 It is controversial whether angiogenesis-targeted therapy holds similar promise in atherosclerotic disease.3 It must be remembered, however, that it has been 35 years since Folkman published his then-heretical hypothesis that tumor growth depended on angiogenesis, 6 and 30 years since Brem and Folkman reported the first-known angiogenesis inhibitor.7 Many of the complex, multigene events of angiogenesis and arteriogenesis in atherosclerotic disease remain to be elucidated.The challenge is all the more difficult because of the diverse pathophysiological mechanisms of those two major kinds of new vascular growth associated with lesion development, one composed mainly of new capillaries, the other the collateral circulation formed by capillaries, arterioles, and arteries.2,4 Bochkov and colleagues in the current issue of Circulation Research distinguish new mechanisms of angiogenesis in atherosclerotic lesions.8 Lipoproteins accumulated in the extracellular space of the intima may be particularly susceptible to oxidative modification because they are not in contact with plasma antioxidants.It is generally agreed that heightened oxidative stress, characterized by lipid and protein oxidation in the vascular wall, is a key factor in atherogenesisThe opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.