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Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

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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.

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Authors and Affiliations

  1. 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

    Samuel Chege Gitau, Xuelian Li, Dandan Zhao, Zhenfeng Guo, Haihai Liang, Ming Qian, Lifang Lv, Tianshi Li, Bozhi Xu, Yong Zhang, Chaoqian Xu, Yanjie Lu, Hongli Shan & Baofeng Yang

  2. Institute of Cardiovascular Research, Harbin Medical University, Harbin, 150081, China

    Zhiguo Wang, Yanjie Lu & Baofeng Yang

  3. Department of Pharmacy and Complementary Medicine, School of Health Sciences, Kenyatta University, P.O. BOX 43844-00100, Nairobi, Kenya

    Samuel Chege Gitau

  4. Institute of Clinical Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, 150081, China

    Zhiming Du

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  1. Samuel Chege Gitau
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  2. Xuelian Li
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Correspondence to Hongli Shan or Baofeng Yang.

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Samuel Chege Gitau and Xuelian Li contributed equally to this work.

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Gitau, S.C., Li, X., Zhao, D. et al. Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling. Front. Med. 9, 444–456 (2015). https://doi.org/10.1007/s11684-015-0421-z

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