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Characterization of the coronary vascular transcriptome in a rat model of metabolic syndrome
Author(s) -
Bender Shawn B,
Davis J. Wade,
Rector R. Scott,
Laughlin M. Harold,
Sowers James R
Publication year - 2013
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.27.1_supplement.lb645
Subject(s) - medicine , endothelial dysfunction , cardiology , insulin resistance , metabolic syndrome , endocrinology , vasodilation , vasoconstriction , transcriptome , insulin , obesity , gene expression , biology , gene , biochemistry
Obesity, insulin resistance and the metabolic syndrome (MetS) cause coronary microvascular dysfunction and defects of coronary flow control. Although myriad mechanisms contribute to this dysfunction no study has comprehensively determined MetS‐associated differential coronary vascular gene expression (the coronary transcriptome). Coronary arteriolar function and gene expression was determined in vessels from obese Otsuka Long‐Evans Tokushima Fatty (OLETF) and lean Long‐Evans Tokushima Otsuka (LETO) rats. Coronary endothelial dysfunction was present in OLETF rats by 5–8wk of age. At 32wk of age, OLETF exhibited obesity, hyperglycemia, and hypertriglyceridemia but normal blood pressure compared to LETO. At this age, coronary arteriolar dysfunction was characterized by vasoconstriction to insulin and impaired dilation to acetylcholine. Vasoconstriction to endothelin‐1 and the thromboxane analog U46619 was increased while constriction to 80mM KCl or the L‐type calcium channel opener BayK 8644 was unchanged. The coronary transcriptome was determined by RNA deep sequencing in OLETF and LETO septal artery samples and revealed dramatic differences in gene expression between groups. This is the first study to comprehensively characterize the coronary transcriptome in an established model of MetS. Supported by NIH HL107910 and HL36088, VHA‐CDA2 IK2BX001299, MU Internal Medicine Research Council.