Molecular Players and Cellular Mechanisms that Govern Cell Behaviour in Adult Angiogenic Sprouting

Abstract

ABSTRACT Blood vessels, guardians of the organism’s global homeostasis, are formed achieved by vasculogenesis and angiogenesis. The present review was aimed at molecular players and cellular mechanisms that govern cell behaviour in adult angiogenic sprouting. Studies were accessed through an electronic web-based search strategy from PubMed, Cochrane Library, Google Scholar, Embase, PsycINFO and CINAHL by using a combination of search terms. In adults, angiogenesis is the most common form of blood vessel formation and also under strict control. Although most blood vessels in an adult organism remain quiescent, endothelial cells retain the capability of rapid division in response to physiological stimuli. Tip cell and stalk cell are two principal cells involved in sprouting angiogenesis. A fine-tuned feed-back loop between VEGF and Notch/Dll-4 signaling pathways is established and a cross-talk between these pathways is essential for proper patterning of the vasculature. Once the tip cell has been selected, filopodia guides the growing sprout towards a gradient of VEGF and other attractive guidance cues. An important first step in any anastomosis is the formation of a stable contact between two ECs. The formation of an interconnected luminal space and the formation of multicellular, perfused tubes in different vascular beds-type I and type II anastomosis-appear to occur at different frequencies. Pruning occurs via two different modes-type I and type II-depending on the state of vessel perfusion during the process. Vessels can adjust their shape and function to meet changing tissue oxygen demands. A fundamental feature of vessel maturation is the recruitment of mural cells. The importance of angiogenesis sparked hopes that manipulating this process could offer therapeutic opportunities.