title: Integrated microRNA and mRNA responses to acute human left ventricular ischemia.
abstract: MicroRNAs (miRNAs) play a significant role in ischemic heart disease. Animal models of left ventricular (LV) ischemia demonstrate a unique miRNA profile; however, these models have limitations in describing human disease. In this study, we performed next-generation miRNA and mRNA sequencing on LV tissue from nine patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. Samples were obtained immediately after aortic cross clamping (baseline) and before aortic cross clamp removal (postischemic). Of 1,237 identified miRNAs, 21 were differentially expressed between baseline and postischemic LV samples including the upregulated miRNAs miR-339-5p and miR-483-3p and the downregulated miRNA miR-139-5p. Target prediction analysis of these miRNAs was integrated with mRNA expression from the same LV samples to identify anticorrelated miRNA-mRNA pairs. Gene enrichment studies of candidate mRNA targets demonstrated an association with cardiovascular disease, cell death, and metabolism. Therapeutics that intervene on these miRNAs and their downstream targets may lead to novel mechanisms of mitigating the damage caused by ischemic insults on the human heart.
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Louis A
authors.initials: LA
authors.lastname: Saddic
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Tzuu-Wang
authors.initials: TW
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Martin I
authors.initials: MI
authors.lastname: Sigurdsson
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Mahyar
authors.initials: M
authors.lastname: Heydarpour
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Stanton K
authors.initials: SK
authors.lastname: Shernan
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sary F
authors.initials: SF
authors.lastname: Aranki
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Simon C
authors.initials: SC
authors.lastname: Body
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; jmuehlschlegel@partners.org.
authors.forename: Jochen D
authors.initials: JD
authors.lastname: Muehlschlegel
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007511:Ischemia / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: mRNA; microRNA; myocardial infarction; sequencing