title: Choline inhibits angiotensin II-induced cardiac hypertrophy by intracellular calcium signal and p38 MAPK pathway.
abstract: Choline, an agonist of M(3) muscarinic acetylcholine receptors, is a precursor and metabolite of acetylcholine and is also a functional modulator of cellular membrane. However, the effect of choline on cardiac hypertrophy is not fully understood. The present study was therefore designed to explore whether choline could prevent cardiac hypertrophy induced by angiotensin II (Ang II) and clarify its potential mechanisms. Cardiac hypertrophy was induced by 0.6 mg kg(-1) day(-1) Ang II for 2 weeks in the presence or absence of choline pretreatment, while cardiomyocyte hypertrophy was induced by Ang II 0.1 μM for 48 h. We found that choline pretreatment attenuated the increment cell size of cardiomyocytes induced by Ang II both in vivo and in vitro. The high ANP and β-MHC levels induced by Ang II were also reversed by choline in cardiomyocytes. Meanwhile, choline pretreatment prevented the augment of reactive oxygen species (ROS) and intracellular calcium concentration in Ang II-treated cardiomyocytes. Furthermore, the upregulated phospho-p38 mitogen-activated protein kinase (MAPK) and calcineurin levels by Ang II in ventricular myocytes were attenuated by choline. In conclusion, choline prevents Ang II-induced cardiac hypertrophy through inhibition of ROS-mediated p38 MAPK activation as well as regulation of Ca(2+)-mediated calcineurin signal transduction pathway. Our results provide new insights into the pharmacological role of choline in cardiovascular diseases.
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang 150081, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Han
authors.forename: Zhen-wei
authors.initials: ZW
authors.lastname: Pan
authors.forename: Peng-zhou
authors.initials: PZ
authors.lastname: Hang
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Sun
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Jiang
authors.forename: Hao-xin
authors.initials: HX
authors.lastname: Song
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000517:prevention & control*; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D060888:Real-Time Polymerase Chain Reaction; D043587:Receptor, Muscarinic M3 / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D043587:Receptor, Muscarinic M3; D000804:Angiotensin II; D048051:p38 Mitogen-Activated Protein Kinases; D019703:Calcineurin; D002794:Choline