Pericyte–Endothelial Interactions

Blood vessels are built and maintained by two interdependent cell types, endothelial cells (ECs) and mural cells. Signals exchanged between these two cell populations control the formation, remodeling, maturation, and function of the vascular network. Pericytes are smooth muscle-like mural cells with unusual properties that play highly dynamic roles in the microvasculature. Inresponse to signals produced by ECs, pericytes invest and partially cover the microvessel wall, where they act to stabilize nascent endothelial tubes, provide essential survival factors, inhibit EC proliferation, and guide vessel wall remodeling. Proper investment of vessel walls with pericytes is a critical and necessary step in vascular development and angiogenesis (Figure 60.1). The purpose of this chapter is to review the multiple roles that endothelial-pericyte interactions play in the development and function of microvessels. PERICYTE INVESTMENT OF MICROVASCULAR ENDOTHELIUM The acquisition of a pericyte coating around microvessels (terminal arterioles, capillaries, post-capillary venules) is referred to as investment (1). The process of investment includes the fundamental steps of cell migration, alignment, contact, and phenotype changes associated with mural cells interacting with ECs. These individual steps overlap in time and are controlled by multiple signaling pathways. Investment of blood vessels with pericytes is a reversible process that is highly responsive to changes in rate and direction of blood flow (2,3). Pericyte investment is mediated by a variety of different factors secreted into the local environment, including plateletderived growth factor (PDGF)-B, angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2), sphingosine-1-phosphate (S1P), transforming growth factor (TGF)-β1, and nitric oxide (NO) (4–9). The microvascular defects in mice with mutations in these secreted pericyte investment factors are summarized later.