Table 2.

Summary of WSS and Stretch/Strain dependent marker expression in TAV and BAV.

Markers	WSS-dependent Expression	Stretch/Strain-dependent Expression	References
Inflammatory Paracrine Signaling	Altered WSS on fibrosa, but not the ventricularis upregulates TGF-β1 & BMP-2 Simultaneous exposure of ventricularis and fibrosa to BAV fused cusp WSS upregulates TGF-β1 & BMP-4	↑ BMP-2, BMP-4 expression with higher cusp stretch; preferentially expressed on fibrosa vs. ventricularis	(31, 69, 74)
Endothelial Activation	ICAM & VCAM are upregulated on fibrosa, but not ventricularis when exposed to altered WSS Simultaneous exposure of ventricularis and fibrosa to BAV fused cusp WSS upregulates ICAM & VCAM	↑ expression of VCAM-1, ICAM-1, & E-selectin in VECs when exposed to sub-physiologic and supraphysiologic strain↑ expression of VCAM-1 in VICs when exposed to sub-physiologic strain	(31, 72, 75, 76)
ECM Remodeling	Exposure to BAV fused cusp WSS upregulates MMP-2, MMP-9, Cathepsin L, and Cathepsin S	↑ expression of MMP-1, MMP-2, MMP-9, cathepsin K, cathepsin S and ↓ expression of cathepsin L in response to higher cusp stretch	(31, 77)
Osteoblast-like Differentiation	Elevated osteocalcin on fibrosa upon exposure to BAV fused cusp WSS	↑ Runx2 expression at higher cusp stretch, preferentially on fibrosa	(31, 74)
NO Signaling	↑ eNOS expression on ventricularis (high magnitude & unidirectional WSS) vs. fibrosa (low & oscillatory)	*	(72)

^*No known reported data to support conclusions.

WSS, wall shear stress; BAV, bicuspid aortic valve; ECM, extracellular matrix; VECs, valve endothelial cells; VICs, valve interstitial cells; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; BMP, bone morphogenic protein; TGF-β, transforming growth factor beta; ICAM, intercellular cell adhesion molecule; VCAM, vascular cell adhesion molecule.