Lp(a) overexpression triggers aortic stenosis in mice
To determine whether Lp(a) can lead to an AS phenotype, leaflets from Lp(a) overexpressing mice fed with high-cholesterol diet were analyzed. There were no deaths in either group. Lp(a) transgenic mice (N=10) demonstrated significant and consistent aortic valve changes including fibrosis (2.0/4 vs 0.5/4), calcification (1.9.4 vs 0.1/4) units, angiogenesis (1.1/4 vs 0.3/4) and inflammatory infiltration (1.0 vs 0.1/4) compared with control aortic valves (N=10; all p<0.001). The fibrosis and calcification was most prominent at the leaflet commissures and at the leaflet free edge (Figure1).Interestingly, non-transgenic mice fed a high-cholesterol diet did show mild valvular fibrotic changes.