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lüll Role of TRPV4 in the Mechanotransduction of Shear Stress in Endothelial Cells Kohler R; Hoyer JTRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades-/-Frontiers in Neuroscience 2007[]; ä (ä): äThe endothelium is a highly specialized multifunctional cell monolayer between blood and tissue. It regulates a variety of vascular functions such as the passage of macromolecules and oxygen supply to organs and tissues, of immune responses, of angiogenesis, and of vascular remodeling. An additional and overall important role of the arterial endothelium is the control of the contractile state of the vascular smooth muscle and thus systemic blood pressure by the release of vasoactive factors. Moreover, endothelial dysfunction contributes to several cardiovascular pathologies such as arteriosclerosis, restenosis disease, vasculitis, or hypertension. The crucial role of the endothelium in the control of vascular tone was first demonstrated by Furchgott and Zawadzki in 1980 [1]. In this pioneer work, they demonstrated that following stimulation with acetylcholine, the endothelium releases a short-lived factor that relaxes the vascular smooth muscle. This factor was later identified as nitric oxide. In addition to humoral stimulation, the endothelium also controls vasodilatation in response to increased hemodynamic forces (i.e., increased shear stress exerted by streaming blood) [2]. This is an important mechanism by which the endothelium controls adequate organ perfusion and protects vessel walls against mechanical damage.ä |