The Role Of Camk2δ-MEF2 Signaling Pathway In Aerobic Exercise-induced Improvement Of Cardiac Function In Hypertension

Abstract

Objective: The purpose of this study was to investigate the effects of aerobic exercise on the Calcium/calmodulin-dependent protein kinase IIδ(CaMKIIδ)-Myocyte enhancer factor-2(MEF2) signaling pathway in SHR myocardial cells, and the role of the A-kinase anchoring protein 150(AKAP150). METHODS: 12-week-old male SHR and WKY rats were randomly assigned to sedentary groups (WKY-SED, SHR-SED) and exercise training groups (WKY-EX, SHR-EX). Exercise groups were performed a 12-week moderate intensity treadmill running. After 12 weeks, the myocardial cells were enzymatically isolated. The experimental methods include HE staining, the Langendorff technique of isolated heart perfusion, immunohistochemistry, immune cell fluorescence, Western blot. RESULTS: 1) After 12 weeks of exercise, SBP in both WKY-EX and SHR-EX were significantly lower than that of their sedentary counterparts. 2) Compared with the WKY-SED group, the SHR-SED group +dp/dtmax, -dp/dtmax significantly decreased, and the SHR-EX group was significantly higher than the SHR-SED group, +dp/dtmax significantly increased, -dp/dtmax decreased (P<0.01), LVSP increased (P<0.01). 3) The fluorescence intensity of CaM and AKAP150 in the SHR-SED group was higher than WKY-SED group (P<0.01), and the fluorescence intensity of the SHR-EX group AKAP150 was higher than SHR-SED group (P<0.01), and the expression of CaM was lower than the SHR-SED group (P<0.01). 4) The protein expression of p-CaMKIIδ, CaMKIIδ and AKAP150 in the SHR-SED group was higher than that in the WKY-SED group (P<0.01). The expression of p-CaMKIIδ/CaMKIIδ, p-HDAC4/HDAC4 and MEF2 of SHR-EX group are lower than the SHR-SED group (P<0.01). The expression of AKAP150 of SHR-EX was higher than SHR-SED group (P<0.01). CONCLUSION: Aerobic exercise reduced the activity of the CaMKIIδ-MEF2 signaling pathway and increased the expression of AKAP150 in the SHR myocardial, which is one of the molecular mechanisms to improve the function of the heart. Key words: cardiac function; CaMKIIδ-MEF2 signaling pathway; aerobic exercise; AKAP150