The Extracellular Matrix as a Modulator of Angiogenesis

TLDR: In this article, it was shown that matrix composition and matrix composition can affect proliferation rate, matrix synthesis, and multicellular organization during the neovascularization process of endothelial cells.

Abstract: Endothelium is comprised of heterogeneous cell populations residing in a variety of vascular beds. The endothelial cells resident in these diverse vascular beds or regions exhibit a broad range of diversity in their functions and appearances in addition to their shared common features such as non-thrombogenicity, polarity, and transport functions. Response to injury (neovascularization) is a response common to all endothelial cell populations, yet the responses vary depending on whether the endothelial cells are derived from large vessels or the microvasculature. Another factor thought to play an important role in the modulation of endothelial cell behavior in response to injury is the extracellular matrix. Large-vessel endothelial cells respond to injury by sheet migration/proliferation until the defect is covered. Evidence has been accrued supporting the concept that the underlying matrix determines, in part, the migration and proliferation rates, possibly via modulating cytoskeletal organization of the cells. In addition, the continual synthesis and secretion of matrix components by the responding cells appear to be crucial in the response to injury. Although microvascular endothelial cells respond to injury by migration and proliferation as do the large vessel endothelial cells, they migrate through interstitial tissue and ultimately form capillaries. Recent evidence has demonstrated that matrix composition can affect proliferation rate, matrix synthesis, and multicellular organization during the neovascularization process. In addition, matrix organization appears to influence differentiation of microvascular endothelial cells, specifically the ability of selected endothelial cell populations to form fenestrations. Thus, matrix composition and organization appear to play significant roles in orchestrating the growth and differentiation of endothelial cells during the highly integrated series of responses known as neovascularization.