Endothelium-derived biologically active substance: von Willebrand factor and endothelin

Abstract

Endothelial cells from the inner lining of the vascular wall and create a continuous nonthrombogenic and semipermeable layer. They are capable of regulating vascular tone, haemostasis, inflammation etc. by synthesis and secretion of various biologically active substances like substance P, acetylcholine, ABO-antigens, endothelium-derived relaxing factor (EDRF), endothelium-derived contracting factor (EDCF), NO, endothelins, thrombospondin, von Willebrand factor and others. In the following review we describe briefly the biology of von Willebrand factor (vWF), a potent adhesive glycoprotein, and the constrictor peptide endothelin, recently isolated from endothelial cell cultures. vWF is the major constituent of FVIII/vWF complex. It is synthesized by endothelial cells and megakaryocytes. Endothelial cell Weibel-Palade bodies act as storage compartments of the large multimeric forms of vWF. Its unique secretion is maintained by constitutive and regulated pathway. vWF is secreted into the lumen and periendothelial matrix and mediates adhesion of platelets to the subendothelium after vascular injury. Structurally defective or immature subunits circulate in the plasma of patients, suffering from von Willebrand disease. Endothelins are a group of 21-aminoacidpeptides secreted mainly by endothelial cells. Synthesis of peptides of the endothelin family is located also in nonendothelial cells like pulmonary and tracheal epithelium, dorsal root ganglia etc. They act as potent vasoactive substances causing sustained elevation of blood pressure as well as powerful bronchoconstrictors, via two distinct receptors. Judging from their physiological effects, they may take part in various diseases like atherosclerosis, hypertension and asthma. The clinical relevance of this is also discussed. Biomedical Reviews 1992; 1: 39-45.