INCREASED CELLULAR EXPRESSION OF MATRIX PROTEINS THAT REGULATE MINERALIZATION IS ASSOCIATED WITH CALCIFICATION OF NATIVE HUMAN AND PORCINE XENOGRAFT BIOPROSTHETIC HEART-VALVES

Dystrophic mineralization remains the leading cause of stenotic or reg urgitant failure in native human and porcine bioprosthetic heart valve s, We hypothesized that cellular expression of noncollagenous matrix p roteins (osteopontin, osteocalcin, and osteonectin) that regulate skel etal mineralization may orchestrate valvular calcification. Porcine bi oprosthetic heart valves and native human heart valves obtained during replacement surgery were analyzed for cells, matrix proteins that reg ulate mineralization, and vessels. Cell accumulation and calcification were correlated for both valve types (rho = 0.75, P = 0.01, native; r ho = 0.42, P = 0.08, bioprosthetic). Osteopontin expression correlated with cell accumulation (rho = 0.58, P = 0.04) and calcification (rho = 0.52, P = 0.06) for bioprosthetic valves, Osteocalcin expression cor related with calcification (rho = 0.77, P = 0.04) and cell accumulatio n (rho = 0.69, P = 0.07) in native valves, Comparisons of calcified ve rsus noncalcified native and bioprosthetic valves for averaged total m atrix protein mRNA signal score revealed increased noncollagenous prot eins mRNA levels in calcified valves (P = 0.07, group I vs. group II; P = 0.02, group III vs. group IV). When stratified according to positi ve versus negative mRNA signal status, both calcified bioprosthetic va lves (P = 0.03) and calcified native valves (P = 0.01) were significan tly more positive for noncollagenous proteins mRNA than their noncalci fied counterparts. Local cell-associated expression of proteins regula ting mineralization suggests a highly coordinated mechanism of biopros thetic and native valve calcification analogous to physiologic bone mi neralization, Modulation of cellular infiltration or cellular expressi on of matrix proteins that regulate mineralization, may offer an effec tive therapeutic approach to the prevention of valve failure secondary to calcification.