Enhancement of Glucose Metabolism via PGC-1α Participates in the Cardioprotection of Chronic Intermittent Hypobaric Hypoxia.

Xuyi Li,Yanming Tian,Huijie Ma,Yue Guan,Yan Liu,Yue Cao,Yi Zhang

doi:10.3389/fphys.2016.00219

Abstract

Background and Aims: Previous studies demonstrated that energy metabolism disturbance impairs cardiac function and chronic intermittent hypobaric hypoxia (CIHH) protects heart against ischemia/reperfusion injury. The present study aimed to test the hypothesis that CIHH protects the heart against ischemia/reperfusion (I/R) injury via improvement of cardiac glucose metabolism.Methods: Male Sprague-Dawley rats received CIHH treatment simulating 5000-m altitude for 28 days, 6 h per day in a hypobaric chamber or no treatment (control). Body weight, fasting blood glucose, blood lipid and glucose tolerance were measured. The left ventricular function of isolated hearts was evaluated during 30 min of ischemia and 60 min of reperfusion using Langendorff method. The mRNA and protein expression involved in cardiac energy metabolism was determined using quantitative PCR and Western blot techniques.Results: 1. There was no difference of body weight, fast blood glucose, blood lipid and glucose tolerance between control and CIHH rats under baseline condition (p > 0.05). 2. The recovery of left ventricular function after I/R was improved significantly in CIHH rats compared to control rats (p < 0.05). 3. The expression of cardiac GLUT4 and PGC-1α was increased but PDK4 gene expression was decreased by CIHH treatment at both mRNA and protein level. Also p-AMPK/AMPK ratio was increased in CIHH rats (p < 0.05).Conclusion: CIHH ameliorates I/R injury through improving cardiac glucose metabolism via upregulation of GLUT4, p-AMPK, and PGC-1α expressions, but downregulation of cardiacPDK4 expression.

Highlights

It is well known that cardiovascular disease is the leading cause of mortality, morbidity, and health care costs globally (Fernando et al, 2015)
The expression of cardiac GLUT4 and PGC-1α was increased but PDK4 gene expression was decreased by chronic intermittent hypobaric hypoxia (CIHH) treatment at both mRNA and protein level
The basal left ventricular functions indicated by Left ventricular developed pressure (LVDP), ±LVdp/dtmax, and left ventricular end diastolic pressure (LVEDP) did not differ between CON and CIHH rats

Summary

Introduction

It is well known that cardiovascular disease is the leading cause of mortality, morbidity, and health care costs globally (Fernando et al, 2015). It has been shown that chronic intermittent hypobaric hypoxia (CIHH), similar to ischemic preconditioning and high altitude hypoxia adaptation, confers cardiac protection against ischemia/reperfusion (I/R) injury in rats (Zhou et al, 2013, 2015; Ma et al, 2014; Bu et al, 2015). The CIHH-induced cardiac protection persists longer than ischemic preconditioning and is associated with fewer side effects, such as polycythemia, right ventricular hypertrophy and pulmonary hypertension compared with long-term adaptation to high-altitude hypoxia (Neckar et al, 2004; Zhang and Zhou, 2012; Bu et al, 2015). Previous studies demonstrated that energy metabolism disturbance impairs cardiac function and chronic intermittent hypobaric hypoxia (CIHH) protects heart against ischemia/reperfusion injury. The present study aimed to test the hypothesis that CIHH protects the heart against ischemia/reperfusion (I/R) injury via improvement of cardiac glucose metabolism

Methods

Results

Conclusion