Vascular endothelium and immune responses: implications for inflammation and angiogenesis

Abstract

ECs are involved in several mechanisms during the immune response, particularly in inflammation. These cells are able to produce vasodilatory mediators and several factors lead to increased vascular permeability. ECs play a central role in leukocyte extravasation, a key feature of inflammation. Several adhesion molecules, termed integrins, selectins, immunoglobulins, and others, act in concert and regulate the sequence of distinct steps. Leukocyte-EC adhesion is regulated by the interactions of receptor-ligand CAM pairs, as well as by soluble mediators, such as proinflammatory cytokines. ECs are active participants in angiogenesis. The outcome of neovascularization is highly dependent on the balance or imbalance between angiogenic mediators and inhibitors. Angiogenic mediators form a complex interactive network that regulates the perpetuation of angiogenesis. Naturally-produced or administered angiostatic agents downregulate the effects of angiogenic factors. There have been several attempts to therapeutically interfere with the cellular and molecular mechanisms described above. Most studies were performed using animal models of various types of inflammation. A limited number of human clinical trials, such as the one using anti-ICAM-1 antibody in RA, had promising results. Specific targeting of pathologic endothelial function may be useful for the future management of various inflammatory diseases.