Layer-Specific Changes in Collagen Fiber Architecture in Calcific Aortic Valve Disease
Extracellular matrix (ECM) “disarray” is a hallmark of calcific aortic valve disease (CAVD). As ECM is known to be a powerful regulator of valvular interstitial cell function, a thorough understanding of ECM “disarray” in CAVD would provide valuable insight into alterations in cellular function. Existing in vitro studies and analyses of native valve tissues have focused almost exclusively on bulk changes in ECM composition, with little attention paid to the nano- and micro- scale architecture where cells directly interact with these structures. In other cell types, fiber organization has been shown to regulate behaviors such as cell polarity, motility, proliferation, and differentiation. Therefore, it is possible that changes in ECM microstructure occurring during CAVD are influencing both biological and mechanical functions of the valve. Second harmonic generation microscopy (SHG) allows for quantification of fibrillar collagen, a major component of the aortic valve architecture, without the use of exogenous treatments. In this study, traditional histology techniques were used together with SHG to characterize the microstructural remodeling of fibrillar collagen in CAVD and investigate potential causes for these architectural changes.