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Brief hypercholesterolemia induces athero‐protective pathways on the patho‐susceptible aortic side endothelium of swine aortic valves
Author(s) -
Guerraty Marie A,
Grant Gregory R,
Karanian John W,
Chiesa Oscar A,
Pritchard Wiiliam F,
Davies Peter F
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.902.12
Subject(s) - medicine , phenotype , aortic valve , endothelium , downregulation and upregulation , cardiology , side effect (computer science) , pathological , endocrinology , gene , biology , biochemistry , computer science , programming language
The aortic valve of humans and swine is preferentially susceptible to calcific sclerosis on the aortic side of the leaflets. Side‐specific endothelial gene expression in normal valves revealed a balance between pro‐pathologic and protective phenotypes on the aortic side (Simmons et al. 2005). We studied the effect of a modest exposure to hypercholesterolemia on the balance of endothelial phenotypes in a side‐specific manner. Eleven adult male swine were fed a normal chow diet (NC; n=6) or an isocaloric high cholesterol diet (HC; n=5) for 2 weeks. Transcript profiles of aortic (A) and ventricular (V) sides of the aortic valves of NC and HC animals were compared. The patho‐susceptible A side showed a markedly greater number of differentially expressed genes than the patho‐protected V side (1325 vs 87; false discovery rate 25%) indicating higher sensitivity to the risk factor on the susceptible side. These phenotypic differences were mirrored at the tissue level with early pathological changes confined to the A side of the leaflets of the HC animals. Pathway analysis showed that the HC treatment decreased TNF and NFkB pathway‐associated gene expression on the A side of the valve relative to the V side, and that a PPARgamma program was activated by the HC treatment on the A side. Together, these findings suggest a risk factor‐driven upregulation of athero‐protective pathways on the susceptible aortic side. NHLBI support.