title: Choline protects against cardiac hypertrophy induced by increased after-load.
abstract: BACKGROUND
  Although inadequate intake of essential nutrient choline has been known to significantly increase cardiovascular risk, whether additional supplement of choline offering a protection against cardiac hypertrophy remain unstudied.
  
  
  METHODS
  The effects of choline supplements on pathological cardiac hypertrophic growth induced by transverse aorta constriction (TAC) for three weeks and cardiomyocyte hypertrophy in cultured cells induced by isoproterenol (ISO) 10 μM for 48 h stimulation were investigated. Western blot analysis and real-time PCR were used to determine the expression of ANP, BNP, β-MHC, miR-133a and Calcineurin.
  
  
  RESULTS
  Administration of 14 mg/kg choline to mice undergone TAC effectively attenuated the cardiac hypertrophic responses, as indicated by the reduced heart weight, left ventricular weight, ventricular thickness, and reduced expression of biomarker genes of cardiac hypertrophy. This anti-hypertrophic efficacy was reproduced in a cellular model of cardiomyocyte hypertrophy induced by isoproterenol in cultured neonatal cardiomyocytes. Our results further showed that choline rescued the aberrant downregulation of the muscle-specific microRNA miR-133a expression, a recently identified anti-hypertrophic factor, and restored the elevated calcineurin protein level, the key signaling molecule for the development of cardiac hypertrophy. These effects of choline were abolished by the M3 mAChR-specific antagonist 4-DAMP.
  
  
  CONCLUSIONS
  Our study unraveled for the first time the cardioprotection of choline against cardiac hypertrophy, with correction of expression of miR-133a and calcineurin as a possible mechanism. Our findings suggest that choline supplement may be considered for adjunct anti-hypertrophy therapy.
authors.affiliation: Institute of Clinical Pharmacology, the Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Yilei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology*; D015536:Down-Regulation; D005819:Genetic Markers; D007545:Isoproterenol; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D005819:Genetic Markers; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D019703:Calcineurin; D007545:Isoproterenol; D002794:Choline
keywords: Calcineurin.; cardiac hypertrophy; cardiomyocyte; choline; miR-133a