Aerobic exercise improves cardiac function in rats with chronic heart failure through inhibition of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1).

Abstract

BackgroundTo explore the beneficial effects and underlying mechanisms of aerobic exercise on chronic heart failure (CHF).MethodsA CHF rat model was induced via left anterior descending coronary artery ligation. Four weeks post-surgery, CHF rats received aerobic exercise training over an 8-week period and cardiac function indexes including xxx were analyzed. To investigate the mechanisms involved in the aerobic exercise-induced benefits on CHF, overexpression of the long non-coding RNA MALAT1 was examined both in vivo and in vitro. Furthermore, the interaction between MALAT1 and the microRNA miR-150-5p and the downstream PI3K/Akt signaling pathway was investigated.ResultsCompared to the control group, the CHF rats showed evidence of left ventricular dysfunction including aggravated cardiac function indexes and lung to body weight ratio. The Masson staining demonstrated a significant degree of blue-stained fibrotic myocardial tissue in CHF rats compared to control rats. Furthermore, the levels of collagen I and collagen II were also markedly increased in CHF rats. Aerobic exercise improved cardiac function and left ventricular remodeling in rats with CHF. There was a significant reduction in the levels of the reactive oxygen species (ROS), inflammatory cytokines including TNF-α, IL-6, and IL-1β, and inflammatory mediums containing the matrix metalloproteinases (MMPs) MMP-2 and MMP-9. Moreover, CHF rats receiving aerobic exercise showed decreased myocardial apoptosis and increased expression of autophagy-related proteins including beclin-1 and LC3B-II. Overexpression of the lncRNA MALAT1 eliminated all the beneficial effects related to aerobic exercise in CHF rats. Subsequent investigations demonstrated that miR-150-5p expression was up-regulated in CHF-Tr rats and down-regulated in CHF-Tr-MALAT1 rats. Furthermore, the downstream PI3K/Akt signaling pathway was re-activated in CHF-Tr-MALAT1 rats. In vitro experiments revealed that overexpression of MALAT1 reduced the miR-150-5p levels, resulting in increased cellular apoptosis and less autophagy. In addition, overexpression of MALAT1 suppressed the downstream PI3K/Akt signaling pathway. Restoring miR-150-5p level with a miR-150-5p mimic decreased the cellular apoptosis and increased autophagy, and the downstream PI3K/Akt signaling pathway was re-activated.ConclusionsAerobic exercise improved cardiac function through inhibition of the lncRNA MALAT1 in CHF, and the potential mechanisms may be mediated via the miR-150-5p/PI3K/Akt signaling pathway.