DIFFERENCES IN TISSUE REMODELING POTENTIAL OF THE AORTIC AND PULMONARY HEART VALVE INTERSTITIAL CELLS

Abstract

Heart valve interstitial cells (VICs) have a plastic and reversible phenotype, possibly attributable for tissue remodeling during times of development and repair. Therefore, we hypothesized that the cytoskeletal (CSK) remodeling capability of the porcine aortic and pulmonary VICs (AVICs and PVICs, respectively), which is dominated by smooth muscle a-actin, would exhibit unique contractile behaviors when seeded on collagen gels. Moreover, we evaluated the initial mechanical state of the underlying CSK by comparing AVIC and PVIC stiffness with atomic force microscopy. AVICs were not only significantly stiffer (p<0.001) than the PVICs, but also contracted the gels significantly more at 24 and 48 hours (p<0.001). Neither VIC population contracted the gels at early time points (2 and 4 hours) as dermal fibroblasts did, but formed a central cluster of cells prior to contraction. After clustering, VICs appeared to radiate out from the center of the gels; fibroblasts did not migrate but contracted the gels locally. VIC gels treated with TGF-beta1 contracted the gels rapidly, revealing similar sensitivity to the cytokine. These findings suggest that the AVICs are capable of inducing greater ECM contraction, possibly resulting in more rapid valvular tissue remodeling. Thus, mechanobiological differences between the AVIC and PVICs may exist.