Regulation of valvular interstitial cell calcification by components of the extracellular matrix.

Understanding the interactions between extracellular matrix (ECM) components and valvular interstitial cells (VICs) is relevant to both treating heart valve disease and designing heart valve tissue engineering scaffolds, yet the VIC-ECM relationship has not been well characterized. Thus, the aim of this study was to characterize VIC-ECM interactions, paying specific attention to whether ECM composition affected the in vitro calcification of VICs. Our results show that the number and size of calcific nodules formed in VIC cultures, as well as the expression of the mineralization markers alkaline phosphatase (ALP) and CBFa1, were highly dependent upon the composition of the culture surface. VICs cultured on certain ECM components, that is, collagen and fibronectin, were resistant to calcification, even upon treatment with mineralization-inducing growth factors. Meanwhile, cultures of VICs on fibrin, laminin, and heparin coatings had a high number of calcified nodules, although only VICs on fibrin expressed significantly elevated levels of ALP and CBFa1. Nodule composition analysis revealed the presence of multiple types of mineralization. Although apoptotic and necrotic cells were more concentrated in nodules, these nodules did contain a strong majority population of viable cells. Characterizing this ECM-dependence of VIC calcification will help us to identify appropriate biomaterial environments for heart valve tissue engineering as well as elucidate mechanisms of valvular disease.