Studying the role of nitric oxide in initiating angiogenesis and its patterning

Abstract

Angiogenesis is a multi-stage process that forms blood vessels. Endothelial cells line the inner most core of the blood vessel. The migration and proliferation of endothelial cells sway the process of angiogenesis. Endothelium derived endogenous or exogenous nitric oxide is known as a key modulator of angiogenesis. Eventually such an investigation leads to two important queries (1) Does quantitative and qualitative effects of nitric oxide are specific to particular stage of angiogenesis? and (2) considering angiogenesis as a multistage process what is the specific effect of nitric oxide on the initial stages of angiogenesis. The first part of this investigation targets the first question wherein; we observed that the half-lives of donors define the bio-availability of nitric oxide in physiological micro-milieu, and guides the formation of blood vessels. The present study elaborates that sperminonoate induces surge and regulation of anigogenic markers such as VEGF, VEGFR2 and Tie2 were maximally responded to sperminonoate by activating cGMP-PKG-VASP pathway. Further, we elucidated the implications of endothelial nitric oxide synthase and NO/sGC/cGMP pathway in the formation of endothelial ring an early phenomenon in angiogenesis. T h e next phase offers first major experimental evidence for elucidating the functional monomeric units of angiogenesis and implications of NO on these biological structures. We conclude that nitric oxide plays a major role in fabricating the blood vessels by acting at different stages of vessel de novo development and maturation. Vascular endothelial cells can form ring-like structures that are specifically being regulated by NO. On one hand this study will help in designing and directing NO based drugs according to specific requirements and on the other it deems to use endothelial rings structures as in vitro models to study angiogenesis. newline newline newline