title: Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling.
abstract: Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction (TAC) or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin (10 mg·kg(-1)·d(-1)); the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II (10 nmol·L(-1)) was treated with the human equivalent of low (10 or 100 μmol·L(-1)) and high (1000 μmol·L(-1)) aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, β-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and b-type natriuretic peptide (BNP). Aspirin efficiently reversed the upregulation of β-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3β. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of β-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin.
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, 150081, China.|Department of Pharmacy and Complementary Medicine, School of Health Sciences, Kenyatta University, P.O. BOX 43844-00100, Nairobi, Kenya.
authors.forename: Samuel Chege
authors.initials: SC
authors.lastname: Gitau
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, 150081, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Li
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, 150081, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
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, 150081, China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Guo
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, 150081, China.
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
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, 150081, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Qian
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, 150081, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Lv
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, 150081, China.
authors.forename: Tianshi
authors.initials: T
authors.lastname: Li
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, 150081, China.
authors.forename: Bozhi
authors.initials: B
authors.lastname: Xu
authors.affiliation: Institute of Cardiovascular Research, Harbin Medical University, Harbin, 150081, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wang
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, 150081, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
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, 150081, China.
authors.forename: Chaoqian
authors.initials: C
authors.lastname: Xu
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, 150081, China.|Institute of Cardiovascular Research, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Institute of Clinical Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Du
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, 150081, China. shanhongli@ems.hrbmu.edu.cn.
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
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, 150081, China. yangbf@ems.hrbmu.edu.cn.|Institute of Cardiovascular Research, Harbin Medical University, Harbin, 150081, China. yangbf@ems.hrbmu.edu.cn.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D016903:Drug Monitoring; D004452:Echocardiography / Q000379:methods; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016861:Cyclooxygenase Inhibitors; D051153:Wnt Proteins; D051176:beta Catenin; D051058:Oncogene Protein v-akt; D001241:Aspirin
keywords: Akt; GSK-3β; Wnt/β-catenin; aspirin; cardiac hypertrophy