Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling
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Date
2015
Authors
Gitau, Samuel C.
Li, Xuelian
Zhao, Dandan
Guo, Zhenfeng
Liang, Haihai
Qian, Ming
Lv, Lifang
Li, Tianshi
Xu, Bozhi
Wang, Zhiguo
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Verlag
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
Description
DOI 10.1007/s11684-015-0421-z
Keywords
Aspirin, Akt, Cardiac hypertrophy, GSK-3β, Wnt/β-catenin
Citation
Front. Med. 2015, 9(4): pp 444–456