Integrin Receptors and the Regulation of Angiogenesis

Abstract

Over the past several years a renewed interest has emerged in the biochemical and molecular mechanisms controlling vascular development and its implications in human disease. This renewed enthusiasm has lead many investigators towards the isolation and identification of molecules that regulate the formation of new blood vessels in hopes that targeting these molecules may provide novel strategies for the treatment of human vascular disorders. In general, the formation of new blood vessels can occur by either of two similar but distinct physiological processes termed “vasculogenesis” and “angiogenesis” (1–4). Vasculogenesis is associated with the development of new blood vessels from precursor cells called angioblasts (3,4) and will not be discussed further in this chapter; instead, we will focus on angiogenesis. Angiogenesis is the process by which a network of new blood vessels form from a pre-existing vascular bed (5,6). This complex process can be characterized by at least three general stages including: initiation by growth factors or cytokines; proteolytic remodeling of the extracellular matrix (ECM) and endothelial-cell migration; and finally, capillary differentiation and maturation (7). These cellular events are tightly regulated and can occur during normal physiological processes such as trophoblast implantation, embryonic development, and wound healing (1–7). However, during certain pathological conditions such as rheumatoid arthritis (RA), diabetic retinopathy, and tumor growth and metastasis, the tightly regulated control mechanisms are disrupted, leading to accelerated vascular growth (1–7). Therefore, the identification and isolation of molecules that regulate angiogenesis will likely facilitate the development of novel approaches for the treatment of human neovascular diseases.