Effects of Adiponectin on Diastolic Function in Mice Underwent Transverse Aorta Constriction

Xueting Han,Juan Cao,Jingfeng Wang,Kai Hu,Aijun Sun,Jingmin Zhou,Yu Song,Yanyan Wang,Junbo Ge,Mingqiang Fu,Xiaotong Cui,Yuyuan Fan,Jie Luo,Yunzeng Zou

doi:10.1007/s12265-019-09913-1

Abstract

Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN). Nevertheless, the effects of APN on diastolic dysfunction in pressure overload model induced by transverse aorta constriction (TAC) remain to be further elucidated. Here, we demonstrated that treatment of APN attenuated diastolic dysfunction and cardiac hypertrophy in TAC mice. Notably, APN also improved active relaxation of adult cardiomyocytes, increased N2BA/N2B ratios of titin isoform, and reduced collagen type I to type III ratio and lysyl oxidase (Lox) expressions in the myocardial tissue. Moreover, APN supplementation suppressed TAC-induced oxidative stress. In vitro, inhibition of AMPK by compound C (Cpc) abrogated the effect of APN on modulation of titin isoform shift and the anti-hypertrophic effect of APN on cardiomyocytes induced by AngII. In summary, our findings indicate that APN could attenuate diastolic dysfunction in TAC mice, which are at least partially mediated by AMPK pathway.

Highlights

Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN)
There were 5 in 30 mice died 1 week after transverse aorta constriction (TAC) and 0 in 12 mice died after sham operation
To further investigate myocardial relaxation on a cellular level and the effect of APN on it, we evaluated cardiac mechanics using adult cardiomyocytes isolated from sham, TAC, and APN-treated mice

Summary

Introduction

Diastolic dysfunction is common in various cardiovascular diseases, which could be affected by adiponectin (APN). The effects of APN on diastolic dysfunction in pressure overload model induced by transverse aorta constriction (TAC) remain to be further elucidated. We demonstrated that treatment of APN attenuated diastolic dysfunction and cardiac hypertrophy in TAC mice. APN improved active relaxation of adult cardiomyocytes, increased N2BA/N2B ratios of titin isoform, and reduced collagen type I to type III ratio and lysyl oxidase (Lox) expressions in the myocardial tissue. Impaired active myocardial relaxation and increased passive stiffness are the two major elements of LV diastolic dysfunction, which jointly lead to elevated LV filling pressure [6]. Clinical studies showed that diastolic dysfunction is an independent risk factor in patents with various cardiovascular diseases including hypertensive patients with left ventricular hypertrophy

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