Cell polarity in the cardiovascular system

The importance of cell polarity asa fundamental biological principle is inc reasingly recognized in the cardiovascular system. Polar cell mechanisms un derlie not only the development of the heart and blood vessels, but also pl ay a major role in the adult organism for polarized endothelial functions s uch as the separation of the intra- and extravascular compartment and the v ectorial exchange of substances between these compartments. Endothelial cel ls are connected through intercellular junctions which separate the functio nally and structurally distinct luminal and abluminal cell surfaces. The-lu minal plasma membrane is in contact with the blood and takes part in the re gulation of hemostasis. The abluminal cell membrane connects the endothelia l cell with the basement membrane and modulates blood flow through the rele ase of vasoactive substances. Results from epithelial model systems have sh own that the polarized cell phenotype is generated by specific protein sort ing and regulated protein trafficking between the trans-Golgi network and t he cell surface. The polarized distribution of cell membrane proteins is ma intained by anchorage with the cytoskeleton and limitation of lateral diffu sion by tight junctions. Disturbances of cell polarity may contribute to th e pathogenesis of disease states, including ischemic and radiocontrast-indu ed acute renal failure and carcinomas. Recent results have demonstrated the importance of cholesterol for protein traffic from the trans-Golgi network to the apical cell membrane. This novel intracellular function of choleste rol could point to a connection between cell polarity and the pathogenesis of arteriosclerosis. The polarity of the endothelium also has to be taken i nto account when developing gene-therapeutic strategies, since therapeutic success will not only depend on the efficient expression of the desired gen e product, but also on its correct cellular location or secretion into the correct extracellular compartment. These examples demonstrate the biologica l and potentially clinical relevance of cell polarity in the cardiovascular system.