Regulation of Blood Flow
Vasodilation and vasoconstriction, the widening and narrowing of blood vessels respectively, are essential processes to controlling blood flow. The endothelium responds to various vasoactive factors to maintain the vascular tone of arteries and veins and achieves this via the contraction or relaxation of the smooth muscle cells which underlie the basal membrane of these vessels. Nitric oxide, produced by many cells in the body, is a vasodilator. Norepinephrine, which functions as a hormone and a neurotransmitter, is a vasoconstrictor. Endothelial cells generate an anti-thrombotic surface that facilitates transit of plasma and cellular constituents throughout the vasculature and maintenance of homeostasis.
Wound Healing
Hemostasis, the process by which bleeding is stopped at the site of an injury while normal blood flow is maintained throughout the circulatory system, is one of the first stages of wound healing. The endothelium is pivotal to this, for example by controlling platelet adhesion and activation and by synthesizing the essential blood clotting protein Factor VIII. Endothelial cells are also involved in fibrinolysis, the dissolution of blood clots once the wound has healed. They can achieve this by secreting tissue-type plasminogen activator (t-PA).
Prevention of Thrombosis
Thrombosis is the abnormal formation of a blood clot within the vasculature which can obstruct blood flow. Although blood clotting is an essential stage of the wound healing process, it can be fatal if allowed to occur in an uncontrolled manner. The endothelium has various anti-thrombotic properties. These include the secretion of prostacyclin which inhibits platelet aggregation, and the storage and release of von Willebrand factor which binds to the clotting protein Factor VIII.
Angiogenesis
Angiogenesis, the formation of new blood vessels, occurs during early embryonic development and continues throughout the entire human lifespan. It is essential to the process of wound healing but has particularly been a subject of interest to researchers who study tumorigenesis. The proliferation and metastasis of cancer cells is dependent on an adequate supply of oxygen and nutrients. Tumor growth is supported by formation of new blood vessels that provide nutrients for these cells to expand. Many cancer therapeutic strategies have targeted tumor angiogenesis in hopes of limiting cancer progression.
The Inflammatory Response
Endothelial cells are key regulators of the inflammatory response since they form a crucial line of defense against infection. Dysregulation of the inflammatory response is implicated in a wide variety of diseases, and researchers have studied many different signaling pathways to advance understanding of the role of endothelial cells in conditions which include atherosclerosis, rheumatoid arthritis and inflammatory bowel diseases.