Regulation of vascular integrity

Abstract

The integrity of blood vessels is critical to vascular homeostasis. Maintenance of vascular integrity has been conventionally regarded as a passive process that is largely dependent on continuous blood flow. Recent studies, however, have begun unveiling molecular processes essential for maintenance of vascular integrity and homeostasis under physiological conditions, leading to the notion that maintenance of the vasculature is an active biological process that requires continuous, basal cellular signaling. Failure of this system results in serious consequences such as hemorrhage, edema, inflammation, and tissue ischemia. In this review, we will discuss the emerging concepts in regulation of vascular integrity with the emphasis on structural components of blood vessels that are essential for vascular maintenance.

Figure 1

Proposed model of VEGF-FGF mediated regulation of EC permeability VEGF increases vascular permeability by Src-dependent phosphorylation of VE-cadherin (right half). FGF may counteract the VEGF effect by two mechanisms: (1) facilitating Csk association with VE-cadherin, thereby inhibiting local Src activation and/or (2) activating VE-cadherin phosphatases such as VE-PTP or PTPμ, by which VE-cadherin stays dephosphorylated at catenin binding sites and stably binds to catenins. p120-catenin binding is critically important for cadherin retention at adherens junctions.