Angiogenesis in Atherosclerosis: An Overview
Angiogenesis, the process of formation of new blood vessels, involves a complex interplay of various growth signals and cellular milieu. It plays an important role in many physiological and pathological processes. The study of angiogenesis has gained mome
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Angiogenesis in Atherosclerosis: An Overview Sadip Pant, Abhishek Deshmukh, and Jawahar L. Mehta
Abstract Angiogenesis, the process of formation of new blood vessels, involves a complex interplay of various growth signals and cellular milieu. It plays an important role in many physiological and pathological processes. The study of angiogenesis has gained momentum from two different perspectives. On the one hand, angiogenesis is essential for physiologic processes such as menstrual bleeding, wound healing, and embryonic development; on the other hand, histopathologic studies suggest that angiogenesis has an important role in the growth of the atherosclerotic plaque and several tumors. From a clinical perspective, drugs that inhibit angiogenesis seem to increase the incidence of thromboembolic events. Recent data suggests that endothelial-derived growth factor (VEGF) constitutes only a small proportion of total body VEGF and does not contribute significantly to the overall angiogenic response. However, such autocrine VEGF signaling is required for endothelial cell survival and maintenance of vascular homeostasis. In parallel, the discovery of VEGF has guided us to therapeutic angiogenesis as a possible treatment for ischemic heart and peripheral disease. Results of numerous preclinical studies have provided evidence that angiogenic growth factors can promote collateral channel development which can reduce ischemia. Nonetheless, clinical trials on therapeutic angiogenesis have not been very impressive as expected. Bench and bedside research continues to bring insight into the mechanisms of tissue ischemia and tumor growth. Further understanding of different facets of angiogenesis may help in the development of novel and specific therapies. Keywords Neovascularization • Atherosclerosis • VEGF • FGF • Arteriogenesis • Therapeutic angiogenesis
S. Pant • A. Deshmukh • J.L. Mehta (*) Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, 4301 West Markham, Little Rock, AR 72205, USA e-mail: [email protected] J.L. Mehta and N.S. Dhalla (eds.), Biochemical Basis and Therapeutic Implications of Angiogenesis, Advances in Biochemistry in Health and Disease 6, DOI 10.1007/978-1-4614-5857-9_12, © Springer Science+Business Media New York 2013
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Introduction
During embryogenesis, angioblasts differentiate into endothelial cells leading to the formation of primary capillary plexus; this process is called vasculogenesis [1]. Vasculogenesis begins very early after the initiation of gastrulation in the mammalian embryo with the formation of angioblast precursors in the mesenchyma. Angiogenesis, unlike vasculogenesis, represents growth of new blood vessels from the preexisting channels. During embryonic development, angiogenesis results in growth and remodeling of the primitive network laid down by vasculogenesis to form an intricate vascular system. Distinct from angiogenesis, arteriogenesis is a process that refers to matur
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