title: Alpha-lipoic acid attenuates cardiac hypertrophy via downregulation of PARP-2 and subsequent activation of SIRT-1.
abstract: Alpha-lipoic acid (ALA) has been described as a therapeutic agent for a number of conditions related to cardiovascular disease. However, its role in protecting against cardiac hypertrophy has not been elucidated. In this study, we found that ALA effectively ameliorated cardiac hypertrophy in vivo and in vitro. The mRNA and protein levels of poly (ADP-ribose) polymerase-2 (PARP-2), which were significantly upregulated in heart tissues of abdominal aortic constriction (AAC) rats and cultured cardiomyocytes exposed to angiotensin II(Ang II), were significantly suppressed by ALA treatment. Furthermore, ALA reversed the downregulation of sirtuin 1 (SIRT1) induced by Ang II. However, when cardiomyocytes were co-transfected with PARP-2 plasmid or siRNA for SIRT1, ALA failed to inhibit hypertrophic responses. These observations suggested that ALA attenuated cardiac hypertrophy, at least partially via inhibition of PARP-2 and subsequent activation of SIRT1. These findings may shed new light on the understanding of the cardioprotective effect of ALA.
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou 730000, PR China; Gansu Province Center for Disease Control and Prevention, Lanzhou 730000, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: People׳s Hospital of Gansu Province, Lanzhou 730000, Gansu, China; Chengdu Fifth People's Hospital, Chengdu 611130, Sichuan, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.affiliation: People׳s Hospital of Gansu Province, Lanzhou 730000, Gansu, China.
authors.forename: Erqing
authors.initials: E
authors.lastname: Chai
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou 730000, PR China. Electronic address: ymzhang@lzu.edu.cn.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000804:Angiotensin II; D008063:Thioctic Acid; C557783:Parp2 protein, rat; D011065:Poly(ADP-ribose) Polymerases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: ALA; Alpha-lipoic acid (PubChem CID: 864); Cardiac hypertrophy; PARP-2; SIRT1