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)

Ling Hu; Ya-Nan Xu; Qian Wang; Mei-Jie Liu; Ping Zhang; Lan-Ting Zhao; Fang Liu; Dong-Yan Zhao; He-Nan Pei; Xing-Bao Yao; Hua-Gang Hu

doi:10.21037/atm-20-8250

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)

Ann Transl Med. 2021 Feb;9(4):340. doi: 10.21037/atm-20-8250.

Authors

Ling Hu¹, Ya-Nan Xu², Qian Wang³, Mei-Jie Liu⁴, Ping Zhang⁵, Lan-Ting Zhao⁵, Fang Liu⁵, Dong-Yan Zhao², He-Nan Pei³, Xing-Bao Yao⁶, Hua-Gang Hu⁷

Affiliations

¹ Department of Internal Medicine, Beijing Xiaotangshan Hospital, Beijing, China.
² Department of Cardiopulmonary Rehabilitation, Beijing Xiaotangshan Hospital, Beijing, China.
³ Department of Sports Rehabilitation, Beijing Xiaotangshan Hospital, Beijing, China.
⁴ Medical Experiment Center, China Academy of Chinese Medical Sciences, Beijing, China.
⁵ Department of Cardiology, Beijing Tsinghua Changgung Hospital affiliated with Tsinghua University, Beijing, China.
⁶ Department of Sports Injury, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, China.
⁷ Research Office, Beijing Xiaotangshan Hospital, Beijing, China.

Abstract

Background: To explore the beneficial effects and underlying mechanisms of aerobic exercise on chronic heart failure (CHF).

Methods: A 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.

Results: Compared 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.

Conclusions: Aerobic 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.

Keywords: Aerobic exercise; chronic heart failure (CHF); metastasis-associated lung adenocarcinoma transcript 1.