title: Dysregulated miR-361-5p/VEGF axis in the plasma and endothelial progenitor cells of patients with coronary artery disease.
abstract: Dysfunction and reduction of circulating endothelial progenitor cell (EPC) is correlated with the onset of cardiovascular disorders including coronary artery disease (CAD). VEGF is a known mitogen for EPC to migrate out of bone marrow to possess angiogenic activities, and the plasma levels of VEGF are inversely correlated to the progression of CAD. Circulating microRNAs (miRNAs) in patient body fluids have recently been considered to hold the potential of being novel disease biomarkers and drug targets. However, how miRNAs and VEGF cooperate to regulate CAD progression is still unclear. Through the small RNA sequencing (smRNA-seq), we deciphered the miRNome patterns of EPCs with different angiogenic activities, hypothesizing that miRNAs targeting VEGF must be more abundant in EPCs with lower angiogenic activities. Candidates of anti-VEGF miRNAs, including miR-361-5p and miR-484, were enriched in not only diseased EPCs but also the plasma of CAD patients. However, we found out only miR-361-5p, but not miR-484, was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-361-5p to the 3'-UTR of VEGF mRNA. Knock down of miR-361-5p not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. Collectively, we discovered a miR-361-5p/VEGF-dependent regulation that could help to develop new therapeutic modalities not only for ischemia-related diseases but also for tumor angiogenesis.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Genome Research Center & Cancer Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hung-Hao
authors.initials: HH
authors.lastname: Lo
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.affiliation: Department of Obstetrics and Gynecology, Hsin-Chu Mackay Memorial Hospital, Hsin-Chu, Taiwan.
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ko-Hsun
authors.initials: KH
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Fong
authors.initials: CF
authors.lastname: Tasi
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tsung-Neng
authors.initials: TN
authors.lastname: Tsai
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007511:Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C575475:MIRN361 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A