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Inhibition of the Wnt signaling pathway contributes to the cardiac protection of exercise training in spontaneously hypertensive rats  

GUO Ji-Feng¹, LI Meng-Wei², SHI Bing-Ye², ZHANG Yi^2,3, LI Na², WANG Hong-Jie^1,2,4,*

¹College of Clinical Medicine, Hebei University, Baoding 071000, China；²College of Basic Medical Sciences, Hebei University, Baoding 071000, China；³Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China；⁴Hebei Provincial Key Laboratory of Skeletal Metabolic Physiology of Chronic Kidney Disease, Baoding 071000, China

Abstract

The objective of this study was to investigate the cardiac protective effect of low-to-moderate intensity exercise training and the role of the Wnt signaling pathway in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto (WKY) rats were randomly divided into 5 groups, namely hypertensive control (SHR-S), hypertensive plus exercise training (SHR-E), normal blood pressure control (WKY-S), normal blood pressure plus exercise training (WKY-E) and SHR-E plus Wnt agonist (SHR-E-Wnt). The rats in SHR-E and WKY-E groups underwent low-to-moderate intensity swimming for 16 weeks, and the rats in SHR-E-Wnt group were injected with Wnt agonist 1 through tail vein 4 weeks before the end of swimming. The blood pressure of rats was measured every week. After exercise training, the left ventricular wall thickness and ejection function were measured by ultrasound cardiogram, myocardial structure and collagen fiber changes were observed by HE staining and Masson staining, and the expression levels of β-catenin and Dishevelled-1 (DVL-1) mRNA and protein in left ventricular myocardium were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The results showed that the body weight was decreased (P < 0.05), blood pressure was increased (P < 0.01), heart weight and ventricular wall thickness were increased (P < 0.01), and the left ventricular ejection function was decreased (P < 0.05) in SHR-S group compared with those in WKY-S group. In addition, the heart structure was damaged, collagen fibers were significantly increased, and the mRNA and protein expressions of β-catenin and DVL-1 in the left ventricle were significantly up-regulated in SHR-S group compared with those in WKY-S group (P < 0.01). Compared with those in SHR-S group, the body weight of SHR-E group did not change significantly (P > 0.05), but the blood pressure was decreased (P < 0.01), heart weight and ventricular wall thickness were diminished, ejection function was increased (P < 0.01), myocardial structure injury was significantly improved, collagen fibers were significantly reduced, and mRNA and protein expression levels of β-catenin and DVL-1 in the left ventricle were significantly down-regulated (P < 0.01) in SHR-E group. Importantly, exercise-induced antihypertensive and cardioprotective effects in SHR were blunted by Wnt agonist. These results suggest that low-to-moderate intensity exercise training exerts cardioprotective effects in SHR, possibly through inhibiting the Wnt signaling pathway.

Key words: exercise training; Wnt signaling pathway; ventricular remodeling; left ventricular function; spontaneously hypertensive rats

Received: 　　Accepted:

Corresponding author: 王红杰　　E-mail: hongjiew68@163.com

DOI: 10.13294/j.aps.2022.0032

Citing This Article：

GUO Ji-Feng, LI Meng-Wei, SHI Bing-Ye, ZHANG Yi, LI Na, WANG Hong-Jie. Inhibition of the Wnt signaling pathway contributes to the cardiac protection of exercise training in spontaneously hypertensive rats  . Acta Physiol Sin 2022; 74 (5): 773-782 (in Chinese with English abstract).