P808The role of Lipoprotein receptors in calcific aortic valve disease


    loading  Checking for direct PDF access through Ovid

Abstract

Calcific Aortic Valve Disease is the number one indication for cardiac valve replacement in the US. The mechanisms of valve calcification are under intense investigation. Mutations in the low-density lipoprotein-related receptor 5 and 6 have been implicated in a number of disease processed in the field of bone, cancer, eye, neurodegenerative disease, congenital heart abnormalities and cardiovascular disease. This study proposes to test the effect of the LDL-Density-Pressure Receptor mechanism on the development of valvular heart disease. To test this hypothesis in an experimental hypercholesterolemia mouse model ApoE-/-,Lrp5-/-,ApoE-/-/Lrp5-/- mice (n=60) were tested. Group I (n=20) normal diet, Group II (n=20) 0.25% chol diet (w/w), for the development of calcification. The aortic valve (AVA) was examined for calcification, and bone matrix markers. Bone formation was assessed by micro Computed Tomography (microCT), Lrp5, Lrp6, and cbfa-1 expression. Echocardiographic measurements were performed using the Vevo mouse echo machine to determine hemodynamic progression with the diets. Echocardiographic Peak Jet Velocity (Control vs cholesterol) ApoE-/-1.6±0.1m/sec vs 1.7±0.1m/sec,Lrp5-/-1.3±0.1m/sec vs 1.56±0.1m/sec, ApoE-/-/Lrp5-/-1.84±0.3m/sec vs 2.03±0.3m/sec, (p>0.05 for all groups). Calcification analysis demonstrates increased in calcification for the ApoE-/-, and ApoE-/-/Lrp5-/- mice in the cholesterol treatments but no evidence in calcification for the Lrp5-/-,cholesterol treatments by MicroCT and Synchotron measurements. RTPCR analysis demonstrates ApoE-/- increase in Runx2 and Lrp5 in the cholesterol treatment(p<0.05)Lrp5-/-no change in Runx2 and no expression of Lrp5 in the cholesterol treatment, ApoE-/-/Lrp5-/- increase in Runx2 and Lrp6 in the cholesterol treatment(p<0.05). This data demonstrates ApoE, Lrp5 and Lrp6 are critical in the development of valve calcification and that a combination of these receptors play a unique role in the development of calcification in the heart valve for the development of valve calcification.

    loading  Loading Related Articles