title: miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging.
abstract: Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging.
authors.affiliation: Guangdong Key Laboratory of Coronary artery disease, Guangdong Cardiovascular Institute and Guangdong General Hospital, Guangzhou, 510100, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Qin
authors.affiliation: School of Medicine, Wuhan University of Science and Technology, Wuhan, 430081, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Lu
authors.affiliation: School of Medicine, Wuhan University of Science and Technology, Wuhan, 430081, China.
authors.forename: Xiamin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Yeying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Zunzhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Coronary artery disease, Guangdong Cardiovascular Institute and Guangdong General Hospital, Guangzhou, 510100, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Tan
authors.affiliation: Guangdong Key Laboratory of Coronary artery disease, Guangdong Cardiovascular Institute and Guangdong General Hospital, Guangzhou, 510100, China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Guangdong Key Laboratory of Coronary artery disease, Guangdong Cardiovascular Institute and Guangdong General Hospital, Guangzhou, 510100, China.|Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D001162:Arteriosclerosis Obliterans / Q000473:pathology; D016922:Cellular Senescence; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects*; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D044966:Anti-Retroviral Agents; D004338:Drug Combinations; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; C558899:lopinavir-ritonavir drug combination; D054322:tat Gene Products, Human Immunodeficiency Virus; D061466:Lopinavir; D019438:Ritonavir
keywords: HIV; antiretroviral therapy; endothelial cells; miR-34a; senescence; vascular aging