title: Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease.
abstract: Endothelial progenitor cells (EPCs) play an important role in vascular repair and maintenance of vascular homeostasis through re-endothelialization and neovascularization. Cardiovascular risk factors that contribute to coronary artery disease (CAD) have been shown to negatively impact EPCs, although the mechanisms are poorly understood. MicroRNAs (miRNAs) which negatively regulate gene expression at the post-transcriptional level have been shown to impact endothelial cell (EC) angiogenic actions, but little is known about their role in modulating EPC function. In this study we first investigated if EPCs expressed EC specific, angiogenesis-related miRNAs; then determined whether the expression of these miRNAs was altered in EPCs from CAD patients as compared with healthy controls. Furthermore, we examined if atorvastatin, known to increase circulating EPC numbers, had any effect on EPC miRNA expression. We found EPCs produced miR-126, miR-130a, miR-221, miR-222 and miR-92a which have thus far been identified as the most important angiogenic miRNAs. Dysregulation of these miRNAs was detected in EPCs from CAD patients and atorvastatin treatment selectively impacted miRNA expression in EPCs. Our data provide evidence that angiogenic miRNAs might play an important role in the control of EPC function, and that their dysregulation might contribute to EPC dysfunction in patients suffering from coronary artery disease. These findings might lead to the development of novel therapeutic modalities for the prevention and treatment of CAD.
authors.affiliation: Division of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Qiuwang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ivana
authors.initials: I
authors.lastname: Kandic
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kutryk
mesh_terms: D000069059:Atorvastatin; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D035683:MicroRNAs / Q000096:biosynthesis*; D018919:Neovascularization, Physiologic; D011758:Pyrroles / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D035683:MicroRNAs; D011758:Pyrroles; D000069059:Atorvastatin