Gene Expression and Collagen Fiber Micromechanical Interactions of the Semilunar Heart Valve Interstitial Cell

Abstract

The semilunar (aortic and pulmonary) heart valves function under dramatically different hemodynamic environments, and have been shown to exhibit differences in mechanical properties, extracellular matrix (ECM) structure, and valve interstitial cell (VIC) biosynthetic activity. However, the relationship between VIC function and the unique micromechanical environment in each semilunar heart valve remains unclear. In the present study, we quantitatively compared porcine semilunar mRNA expression of primary ECM constituents, and layer- and valve-specific VIC-collagen mechanical interactions under increasing transvalvular pressure (TVP). Results indicated that the aortic valve (AV) had a higher fibrillar collagen mRNA expression level compared to the pulmonary valve (PV). We further noted that VICs exhibited larger deformations with increasing TVP in the collagen rich fibrosa layer, with substantially smaller changes in the spongiosa and ventricularis layers. While the VIC-collagen micro-mechanical coupling varied considerably between the semilunar valves, we observed that the VIC deformations in the fibrosa layer were similar at each valve's respective peak TVP. This result suggests that each semilunar heart valve's collagen fiber microstructure is organized to induce a consistent VIC deformation under its respective diastolic TVP. Collectively, our results are consistent with higher collagen biosynthetic demands for the AV compared to the PV, and that the valvular collagen microenvironment may play a significant role in regulating VIC function.

Quantification and simulation of layer-specific mitral valve interstitial cells deformation under physiological loading

“…Moreover, the predicted local AVIC and overall tissue peak stretches were 1.053/1.014 in the circumferential direction and 1.655/1.500 in the radial direction, showing that the AVIC almost follows tissue deformations; however, the MVIC and tissue-level peak stretches our model predicted were 1.126/1.188 in the circumferential direction and 1.127/1.422 in the radial direction, indicating that the MVIC are significantly different from the tissue-level deformations. Moreover, it was also found in the previous study on the semilunar heart valves (Carruthers et al, 2012a) that the NAR of the aortic VICs in the fibrosa layer reached a saturated value of 5.95 at the maximum transvalvular pressure, whereas the pulmonary VICs in the fibrosa layer underwent significantly greater changes in cellular deformation and reached a NAR of 9.66 at the maximum transvalvular pressure. While the underlying mechanobiology has not been fully understood, this observation along with the findings from this study suggest that the microenvironment of the fibrosa layer provides additional stress shielding for the VICs under high tissue stresses in the MV leaflets compared to those VICs in the semilunar heart valves.…”

Prediction of matrix-to-cell stress transfer in heart valve tissues

“…Using triads of VIC nuclei as fiducials, local strains calculated at a uniaxially applied tissue-level strain of 30% only reached~10% and~20% under circumferential and radial stretches, respectively. Nevertheless, while studies have begun to address the influence of mechanical stretch on in vitro cultured VICs [24,26,[52][53][54][55] and explanted leaflet tissues [19,20], comparatively few studies have investigated the micromechanical interactions between the VICs and ECM in situ [13,56], in order to quantify regional stress distributions associated with the heterogeneous ECM or the stress-strain state of an individual VIC.…”

Interlayer micromechanics of the aortic heart valve leaflet

“…A rectangular model geometry was used, set to 14 mm in length (circumferential direction) by 3 mm in width (radial) by 0.4 mm thick. The tissue layer geometry was derived on previous histological data (Carruthers et al, 2012), which showed that the fibrosa represented 45% of the volume, the spongiosa 30%, and ventricularis 25%. Boundary conditions simulating three-point bending were avoided to ensure no point-loading effects would occur in the center of tissue and end-loading conditions were used instead.…”

“…1-b) (Thubrikar, 1990, Sacks et al, 1998, Schoen and Levy, 1999, Yacoub and Cohn, 2004, Stephens et al, 2008, Wiltz et al, 2013). Each layer contains varying amounts of collagen, glycosaminoglycan (GAG), and elastin (Carruthers et al, 2012). The AV valve has multiple biomechanical properties crucial to enabling proper function (Thubrikar et al, 1977, Missirlis and Chong, 1978, Thubrikar et al, 1979, Sacks et al, 2009).…”