Tianjin Medical Journal

Tianjin Medical Journal ›› 2020, Vol. 48 ›› Issue (1): 38-44.doi: 10.11958/20190267

Previous Articles     Next Articles

The role and mechanism of Akt-Kv4.3-CaMKII in aerobic exercise inhibited pressure overload-induced cardiac hypertrophy

GE Guang-quan1, ZHAO Feng2, CHEN Dao-hu1, SHI Zhen-su1, CHEN Ze-lun1, WANG Tian-guang1, HE Shu-wu1, WEI Yi-zhen3△   

  1. 1 Department of Cardiovascular Surgery, the Second Affiliated Hospital, Hainan Medical College, Haikou 570311, China; 2 Department of Hand Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 3 Department of Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences △Corresponding Author E-mail: weiyizhen@sohu.com
  • Received:2019-01-25 Revised:2019-07-22 Published:2020-01-15 Online:2020-01-15

PDF (PC)

4711

Abstract: Objective To investigate the role and mechanism of serine / threonine kinase (Akt) - ion channel Kv4.3 (Kv4.3) - calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) signaling pathway in aerobic exercise inhibited pressure overload-induced cardiac hypertrophy. Methods Sixty mice were divided into five groups: Sham group, transverse aortic constriction (TAC) group, SHAM+ aerobic exercise (E) group, TAC + E group and TAC+ E + AKt inhibitor perifosine (Peri) group. Transthoracic echocardiography was used to assess the cardiac function and extent of myocardial hypertrophy. The cross-sectional area of myocardial cells was measured by WGA staining. The mRNA expression of ANP was detected by RTqPCR. The protein expression levels of ANP, p-AKt, Kv4.3 and p-CaMKⅡ were detected by Western-blot assay. Results Compared with Sham group, the cardiac function of mice was deteriorated in TAC group (P＜0.01), and the extent of cardiac hypertrophy was increased (P＜0.01). After aerobic exercise training, the cardiac function was improved in TAC + E group, and the level of myocardial hypertrophy was alleviated compared with TAC group (P＜0.01). Western-blot assay showed that the expressions of p-AKT and Kv4.3 were down-regulated, p-CaMKⅡ was up-regulated in TAC group than those in Sham group (P＜0.01). However, the expressions of p-AKT and Kv4.3 were higher, p-CaMKⅡ was lower in TAC+E group than those in TAC mice (P＜0.01). Furthermore, pretreatment with the AKT inhibitor perifosine, deteriorated cardiac function, augmented myocardial hypertrophy and ANP, increased cross-sectional area were observed in TAC+E+Peri group compared with those of TAC+E group (P＜0.01). Meanwhile, the downregulation of p-AKT、Kv4.3 and upregulation p-CaMKⅡ were detected in the TAC+E+Peri group compared with the TAC+E group. Conclusion Aerobic exercise training can inhibit pressure overload-induced cardiac hypertrophy by regulating Akt-Kv4.3-CaMKⅡ.

Key words: cardiomyopathy, hypertrophic, protein-serine-threonine kinases, calcium-calmodulin-dependent protein kinase type 2, disease models, animal, aerobic exercise, Kv4.3