title: Inhibition of MiR-92a May Protect Endothelial Cells After Acute Myocardial Infarction in Rats: Role of KLF2/4.
abstract: BACKGROUND This study was designed to investigate the effects of microRNA-92 (miR-92), Kruppel-like factor 2 (KLF2), and Kruppel-like factor 4 (KLF4) on endothelial injury after acute myocardial infarction (AMI). MATERIAL AND METHODS Blood samples were collected from 50 AMI patients for detection of cardiac troponin I (cTnI), heart-type fatty acid-binding protein (H-FABP), and von Willebrand factor (vWF). The Sprague-Dawley rat models of AMI (n=30) were established by ligating their left anterior descending coronary artery. The cardiac markers of AMI patients and rat models were analyzed with enzyme-linked immunosorbent assay and immunohistochemistry. Human umbilical vein endothelial cells were processed into 5 groups: control, negative control, miR-92a inhibitors, miR-92a inhibitors + KLF2 small interfering RNA (siRNA), and miR-92a inhibitors + KLF4 siRNA. Cell proliferation and apoptosis were detected using MTT assay and flow cytometry. RT-PCR and Western blot were conducted to analyze KLF2 and KLF4 expressions. RESULTS AMI patients exhibited significantly higher expression of both endothelial injury markers (e.g., cTnI, H-FABP, vWF) and miR-92a in blood samples, when compared with controls (P<0.05). Model rats also had similar expressional tendencies, along with lower KLF2 and KLF4 expressions (P<0.05). Further, it could be observed in cellular experiments that treatment of miR-92a mimics can further upregulate endothelial injury markers, and miR-92a and both KLF2 and KLF4 were downregulated by miR-92a mimics (all, P<0.05). Also, the luciferase activity assay confirmed the direct binding of miR-92a to 3' UTR of KLF2/4. CONCLUSIONS MiR-92a was involved in the endothelial injury process after AMI and was able to suppress KLF2 and KLF4 expression.
authors.affiliation: Department of Clinical Laboratory Medicine, The Central Hospital of Nanyang, Nanyang, Henan, China (mainland).
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.affiliation: Cell Morphology Inspection of Clinical Laboratory Medicine, The Central Hospital of Nanyang, Nanyang, Henan, China (mainland).
authors.forename: Guofen
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
authors.forename: Wenxue
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Cardiopulmonary Exercise Testing, The Central Hospital of Nanyang, Nanyang, Henan, China (mainland).
authors.forename: Yibo
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019210:Troponin I / Q000378:metabolism; D015854:Up-Regulation; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; C096161:KLF2 protein, human; C000715467:KLF4 protein, human; C543921:Klf2 protein, rat; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C541874:MIRN92 microRNA, human; C000592377:MIRN92 microRNA, rat; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019210:Troponin I; D014841:von Willebrand Factor