Sex-Specific Features of Calcific Aortic Valve Disease

Figures

• 

  Figure 1. The development of valvular phenotypes in men and women with calcific aortic valve disease (CAVD) with underlying pathogenetic pathways. Summary image depicting CAVD progression in male and female. Normal aortic valve leaflet structure (fibrosa, spongiosa, and ventricular) with valvular interstitial cells (VICs) distributed in all three layers and a monolayer of valve endothelial cells (VECs) covering both sides. Aortic valve sclerosis (AVS) with normal hemodynamics (aortic jet velocity <2.5 m/s) is characterized by: (a) endothelial damage; (b) lipids infiltration and oxidation; (c) T-cell and monocyte infiltration and macrophage differentiation; (d) VIC activation; (e) endothelial to mesenchymal transition (EndMT); and (f) fibrosis and calcium nodule formation. Severe aortic valve stenosis (AS) has significant hemodynamic perturbations: (i) aortic jet velocity > 4.0 m/s; (ii) mean gradient > 40 mmHg; (iii) aortic valve area < 1.0 cm2; (iv) aortic valve area index to body surface < 0.60 cm2/m2. AS is characterized by: (a) endothelial damage; (b) lipids infiltration and oxidation; (c) T-cell and monocyte infiltration and macrophage differentiation; (d) activated and osteogenic…

• 

  Figure 2. Sex-dependent differences in LVH phenotypes in men and women. Summary image depicting the effect of severe AS in men and women on LVH progression. LVH might correlate with severity of AS. Left ventricular remodeling and diffuse interstitial fibrosis increase during the AS progression. For a similar severity of AS, men show more advanced LV remodeling with larger indexed volumes, mass, mass/volume, lower ejection fraction, and more focal fibrosis, while women show higher prevalence of normal geometry or concentric remodeling with higher ejection fraction but relatively higher wall thickness.

• 

  Figure 3. Sex-related signaling pathways in aortic valve fibro-calcification. The diagram represents the known sex differences observed in the signaling pathways implicated in calcific aortic valve disease (CAVD) pathogenesis and progression. Blue lines represent the male specific signaling pathway, red lines represent the female specific signaling pathways, while green lines represent generic signaling pathways.