title: The association between circulating microRNA levels and coronary endothelial function.
abstract: Human microRNAs (miRs) have been implicated in human diseases presumably through the downregulation and silencing of targeted genes via post-translational modifications. However, their role in the early stage of coronary atherosclerosis is not known. The aim of this study was to test the hypothesis that patients with early atherosclerosis and coronary endothelial dysfunction (CED) have alterations in transcoronary miR gradients. Patients underwent coronary angiography and endothelial function testing in the cardiac catheterization laboratory. Patients were divided into abnormal (n = 26) and normal (n = 22) microvascular coronary endothelial function based on intracoronary response to infused acetylcholine measured as a percent change in coronary blood flow (CBF) and arterial diameter. Blood samples were obtained simultaneously from the aorta and coronary sinus at the time of catheterization for RNA isolation, and miR subsequently assessed. Baseline characteristics were similar in both groups. Patients with microvascular CED displayed transcoronary gradients significantly elevated in miR-92a and miR-133 normalized to C-elegans-39 miR. Percent change in CBF and the transcoronary gradient of miR-133 displayed a significant inverse correlation (r2 = 0.11, p = 0.03). Thus, we present novel data whereupon selected miRs demonstrate elevated transcoronary gradients in patients with microvascular CED. The current findings support further studies on the mechanistic role of miRs in coronary atherosclerosis and in humans.
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: R Jay
authors.initials: RJ
authors.lastname: Widmer
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Chung
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Joerg
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged
chemical_list: C548234:MIRN133 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs