Hypercholesterolemia induces side-specific phenotypic changes and peroxisome proliferator-activated receptor-gamma pathway activation in swine aortic valve endothelium.

Arteriosclerosis, Thrombosis, and Vascular Biology
Marie A GuerratyPeter F Davies

Abstract

Background- The endothelium of healthy aortic valves expresses different phenotypes on the aortic and ventricular sides. On the aortic side, which is susceptible to aortic valve sclerosis, there is a balanced coexpression of both propathological and protective pathways. Side-specific global gene expression can address endothelial phenotype balance in early aortic valve sclerosis. Adult male swine were fed a hypercholesterolemic or an isocaloric normal diet for 2-week and 6-month periods. Hypercholesterolemia induced localized lipid insudation confined to the aortic side of the leaflet. Transcript profiling of valve endothelial populations showed that the susceptible aortic side was more sensitive to 2-week hypercholesterolemia than the ventricular side (1,325 vs 87 genes were differentially expressed). However, greater sensitivity was not evidence of a dysfunctional phenotype. Instead, pathway analyses identified differential expression of caspase 3-, peroxisome proliferator-activated receptor gamma-, TNF-alpha-, and nuclear factor-kappaB-related pathways that were consistent with a protective endothelial phenotype. This was confirmed at the protein level at 2 weeks and persisted at 6 months. In a large animal model at high spa...Continue Reading

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Citations

Jun 10, 2010·Seminars in Thrombosis and Hemostasis·Peter F DaviesAnthony G Passerini
Oct 30, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Gretchen J MahlerJonathan T Butcher
Jan 5, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Yi ChuDonald D Heistad
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Jul 28, 2011·International Journal of Inflammation·Gretchen J Mahler, Jonathan T Butcher
Feb 18, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Peter F Davies, Marie A Guerraty
Jul 9, 2013·Circulation Research·Sarah T GouldKristi S Anseth
Aug 29, 2013·Annals of Biomedical Engineering·Emily J Farrar, Jonathan T Butcher
Jul 27, 2011·Journal of Cardiovascular Translational Research·Joyce Bischoff, Elena Aikawa
May 28, 2021·Frontiers in Cardiovascular Medicine·Petra BüttnerFlorian Schlotter
Jul 2, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Zahra Alvandi, Joyce Bischoff
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