Aortic Valve Calcification is Mediated by a Differential Response of Aortic Valve Interstitial Cells to Inflammation

Abstract

Mechanisms of inflammation have been implicated in the pathogenesis of calcific aortic stenosis. In response to pro-inflammatory stimulation via toll-like receptor 4 (TLR-4), the aortic valve interstitial cell (VIC) undergoes a phenotypic change from that of a myofibroblast to that of an osteoblast-like cell. This osteogenic phenotype is characterized by the production of bone-forming proteins like bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP). The aortic valve commonly calcifies, while the other three heart valves do so rarely. We therefore hypothesized that mechanisms of inflammation induce an osteogenic phenotype in aortic VICs but not the VICs from the mitral or right-sided heart valves. Using isolated human VICs from normal aortic, mitral, pulmonary and tricuspid valves, our purpose was to examine and compare the osteogenic response to pro-inflammatory stimulation via TLR-4.