title: Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models.
abstract: Recent evidence suggests that polydatin (PD), a resveratrol glucoside, may have beneficial actions on the cardiac hypertrophy. Therefore, the current study focused on the underlying mechanism of the PD anti-hypertrophic effect in cultured cardiomyocytes and in progression from cardiac hypertrophy to heart failure in vivo. Experiments were performed on cultured neonatal rat, ventricular myocytes as well as adult mice subjected to transverse aortic constriction (TAC). Treatment of cardiomyocytes with phenylephrine for three days produced a marked hypertrophic effect as evidenced by significantly increased cell surface area and atrial natriuretic peptide (ANP) protein expression. These effects were attenuated by PD in a concentration-dependent manner with a complete inhibition of hypertrophy at the concentration of 50 µM. Phenylephrine increased ROCK activity, as well as intracellular reactive oxygen species production and lipid peroxidation. The oxidizing agent DTDP similarly increased Rho kinase (ROCK) activity and induced hypertrophic remodeling. PD treatment inhibited phenylephrine-induced oxidative stress and consequently suppressed ROCK activation in cardiomyocytes. Hypertrophic remodeling and heart failure were demonstrated in mice subjected to 13 weeks of TAC. Upregulation of ROCK signaling pathway was also evident in TAC mice. PD treatment significantly attenuated the increased ROCK activity, associated with a markedly reduced hypertrophic response and improved cardiac function. Our results demonstrated a robust anti-hypertrophic remodeling effect of polydatin, which is mediated by inhibition of reactive oxygen species dependent ROCK activation.
authors.affiliation: Medical College, Shenzhen University, Shenzhen 518000, Guangdong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Ding
authors.affiliation: Cardiology Division, Department of Medicine, The University of Hongkong, Hong Kong, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Anatomy, Hebei Medical University, Hebei 050017, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Shenzhen University, Shenzhen 518060, China.
authors.forename: Dewen
authors.initials: D
authors.lastname: Yan
authors.affiliation: Medical College, Shenzhen University, Shenzhen 518000, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical College, Shenzhen University, Shenzhen 518000, Guangdong, China.
authors.forename: Rongming
authors.initials: R
authors.lastname: Wang
authors.affiliation: Medical College, Shenzhen University, Shenzhen 518000, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Medical College, Shenzhen University, Shenzhen 518000, Guangdong, China.
authors.forename: Shuaiye
authors.initials: S
authors.lastname: Liu
authors.affiliation: Medical College, Shenzhen University, Shenzhen 518000, Guangdong, China. Electronic address: ljljz@yahoo.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D013267:Stilbenes; C472610:atrial natriuretic peptide, rat; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D054460:rho-Associated Kinases; C058229:polydatin
keywords: Hypertrophy; Polydatin; Reactive oxygen species; Rho activity