Matrix Gla protein regulates calcification of the aortic valve.

ABSTRACT

BACKGROUND: The aortic valve interstitial cell (AVIC) has been implicated in the pathogenesis of aortic stenosis. In response to proinflammatory stimulation, the AVIC undergoes a phenotypic change from that of a myofibroblast phenotype to that of osteoblast-like cell. Matrix Gla-protein (MGP) has been identified as an important inhibitor of vascular calcification. We therefore hypothesized that MGP expression is reduced in diseased AVICs, and loss of this protective protein contributes to calcification of the aortic valve. Our purpose was to compare MGP expression in normal versus diseased AVICs. MATERIALS AND METHODS: Human AVICs were isolated from normal aortic valves from explanted hearts (n = 6) at the time of heart transplantation. AVICs were also isolated from calcified, diseased valves of patients (n = 6) undergoing aortic valve replacement. AVICs were grown in culture until they reached passages 2-6 before experimentation. Immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to compare levels of MGP in normal and diseased AVICs. Statistics were performed using the Mann-Whitney U test (P < 0.05). RESULTS: MGP expression was significantly decreased in diseased AVICs relative to normal AVICs by immunofluorescent staining, reverse transcriptase-polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay. CONCLUSIONS: An important anti-calcification defense mechanism is deficient in calcified aortic valves. MGP expression is significantly lower in diseased relative to normal AVICs. Lack of this important "anti-calcification" protein may contribute to calcification of the aortic valve.