Angiogenesis and Atherosclerosis

Among the most exciting developments in vascular medicine is the targeting of specific molecular regulators of blood vessel growth and development for therapeutic benefit. Angiogenesis, whether physiological, such as occurs during embryogenesis, or pathological, such as occurs during wound healing and tumor progression, requires a highly coordinated series of events that includes endothelial cell proliferation, migration, tube and lumen formation, and in some cases, recruitment of smooth muscle and other adventitial cells. A large number of studies in cellular systems and animal models have led to identification and characterization of specific factors that can either stimulate or inhibit angiogenesis.1 These studies were mainly stimulated by Folkman’s hypothesis that tumor growth beyond a few millimeters requires recruitment and formation of a new microcirculation, and thus, that blood vessel–directed therapy might be effective in treating cancer. Translational research has now been initiated by several groups to test the hypothesis that local delivery of angiogenic agents, such as vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), by various strategies, including viral vectors, naked DNA, or purified recombinant proteins, may improve blood flow to ischemic tissues in patients with advanced atherosclerosis. In some cases, preliminary data have been reported and appear promising.2 Specific antiangiogenic therapies are also now in the clinical-trial stage for a broadening group of common diseases, including cancer, macular degeneration, and rheumatoid arthritis. Recent studies in rodent models suggest that antiangiogenic agents may limit adipose mass in hereditary obesity and may slow progression of atheroma.3 The latter result, reported in the April 6, 1999, issue of Circulation , showed that atheromatous lesions beyond a certain size, like malignant tumors, contain an increased number of vasa vasorum and that 2 different angiogenesis inhibitors, the fumagillin analogue TNP-470 or endostatin, a proteolytic fragment of collagen XVIII, when …