Understanding vascular endothelium: nature's container for blood

The entire cardiovascular system, from the chambers of the heart to the smallest capillaries of peripheral tissues, is lined by a single-cell-thick continuous layer-the vascular endothelium. For many years, this gossamer membrane was thought to function largely as an inert barrier, passively separating the reactive components of the circulating blood from the cells and connective tissue matrix of the various organs of the body. With the advent of endothelial cell culture, enabling its isolation and study under experimentally controlled conditions in vitro, a rich appreciation of the dynamic nature of endothelium has emerged. A source of potent bioactive substances, such as prostaglandins, nitric oxide, chemokines and growth factors, the endothelium "speaks" outward to circulating blood elements, such as leukocytes and platelets, and inward to pericytes and smooth muscle cells, modifying their behavior via paracrine signaling mechanisms important in local tissue homeostasis. In response to proinflammatory cytokines (e.g., interleukin-1 and tumor necrosis factor) and bacterial products (e.g., endotoxins), endothelial cells can undergo dramatic phenotypic modulation, manifested by the expression of inducible cell surface adhesion molecules that selectively recruit leukocytes as part of the immune/inflammatory response. Dysregulation of these reactive mechanisms can result in chronic pathologies, such as atherosclerosis and its thrombotic sequelae-heart attack and stroke. The application of high-throughput genomic analyses is revealing the underlying mechanisms of endothelial dysfunction, and pointing the way to new therapeutic strategies in cardiovascular disease.