P5092High extracellular calcium induced valvular calcification through a calcium sensing receptor dependent mechanism

Background: Calcific Aortic Valve Disease (CAVD) is one of the major leading causes of cardiovascular morbidity and mortality. The only treatment available remains valve replacement which is not the safer choice in elderly patients. So far, little is known about the pathophysiological mechanism and the clinical makers associated with CAVD. Valvular calcification (VC) is a key step in the development of CAVD and increased concentration of calcium in the valve microenvironment might play a crucial role in VC. Purpose: To focus on the effect of high extracellular calcium on the progression of CAVD and the possible involvement of calcium sensing receptor (CaSR) in these effects. Methods: Human valvular interstitial cells (hVICs) were isolated from the non-calcified parts of CAVD patients' tricuspid aortic valves. These cells were treated either with calcium (5mM) alone, or with calcium and calcimimetic NPS R-568 (100 nM), or with calcium and calcilytic NPS 2143 (100nM). To confirm the CaSR implication in the calcification process, hVICs cells were transfected with empty (E), wild type (WT) and dominant negative (DN) CaSR plasmids (5μg/well). Furthermore, CaSR siRNA (30nM) was used to downregulate CaSR expression. Finally, CaSR expression was assessed in the calcified and non-calcified parts of human aortic valves.