Fibrotic Aortic Valve Stenosis in Hypercholesterolemic/Hypertensive Mice

Arteriosclerosis, Thrombosis, and Vascular Biology
Yi ChuDonald D Heistad

Abstract

Hypercholesterolemia and hypertension are associated with aortic valve stenosis (AVS) in humans. We have examined aortic valve function, structure, and gene expression in hypercholesterolemic/hypertensive mice. Control, hypertensive, hypercholesterolemic (Apoe(-/-)), and hypercholesterolemic/hypertensive mice were studied. Severe aortic stenosis (echocardiography) occurred only in hypercholesterolemic/hypertensive mice. There was minimal calcification of the aortic valve. Several structural changes were identified at the base of the valve. The intercusp raphe (or seam between leaflets) was longer in hypercholesterolemic/hypertensive mice than in other mice, and collagen fibers at the base of the leaflets were reoriented to form a mesh. In hypercholesterolemic/hypertensive mice, the cusps were asymmetrical, which may contribute to changes that produce AVS. RNA sequencing was used to identify molecular targets during the developmental phase of stenosis. Genes related to the structure of the valve were identified, which differentially expressed before fibrotic AVS developed. Both RNA and protein of a profibrotic molecule, plasminogen activator inhibitor 1, were increased greatly in hypercholesterolemic/hypertensive mice. Hyperchol...Continue Reading

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Citations

Feb 17, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Jeffrey J HsuYin Tintut
Sep 29, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Jacqueline S DronRobert A Hegele
Jul 2, 2018·Journal of the American Heart Association·Robert M WeissDonald D Heistad
Feb 18, 2017·Circulation Research·Ana M PorrasKristyn S Masters
Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Nov 16, 2021·Journal of the American Heart Association·Christiane OttJana Grune

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