Hu Ling, Xu Ya-Nan, Wang Qian, Liu Mei-Jie, Zhang Ping, Zhao Lan-Ting, Liu Fang, Zhao Dong-Yan, Pei He-Nan, Yao Xing-Bao, Hu Hua-Gang
Department of Internal Medicine, Beijing Xiaotangshan Hospital, Beijing, China.
Department of Cardiopulmonary Rehabilitation, Beijing Xiaotangshan Hospital, Beijing, China.
Ann Transl Med. 2021 Feb;9(4):340. doi: 10.21037/atm-20-8250.
To explore the beneficial effects and underlying mechanisms of aerobic exercise on chronic heart failure (CHF).
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 and . Furthermore, the interaction between MALAT1 and the microRNA miR-150-5p and the downstream PI3K/Akt signaling pathway was investigated.
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. 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.
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.
探讨有氧运动对慢性心力衰竭（CHF）的有益作用及潜在机制。
通过结扎左冠状动脉前降支诱导建立CHF大鼠模型。术后4周，CHF大鼠接受为期8周的有氧运动训练，并分析包括xxx在内的心脏功能指标。为研究有氧运动对CHF有益作用的相关机制，检测了长链非编码RNA MALAT1的过表达情况。此外，还研究了MALAT1与微小RNA miR-150-5p以及下游PI3K/Akt信号通路之间的相互作用。
与对照组相比，CHF大鼠表现出左心室功能障碍，包括心脏功能指标恶化和肺与体重比值升高。Masson染色显示，与对照大鼠相比，CHF大鼠心肌组织有明显的蓝色纤维化。此外，CHF大鼠中I型和II型胶原蛋白水平也显著升高。有氧运动改善了CHF大鼠的心脏功能和左心室重塑。活性氧（ROS）、包括肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β在内的炎性细胞因子以及含有基质金属蛋白酶（MMP）-2和MMP-9的炎性介质水平均显著降低。此外，接受有氧运动的CHF大鼠心肌细胞凋亡减少，自噬相关蛋白包括beclin-1和LC3B-II的表达增加。lncRNA MALAT1的过表达消除了有氧运动对CHF大鼠的所有有益作用。随后的研究表明，miR-150-5p在CHF-Tr大鼠中表达上调，在CHF-Tr-MALAT1大鼠中表达下调。此外，CHF-Tr-MALAT1大鼠的下游PI3K/Akt信号通路被重新激活。实验表明，MALAT1的过表达降低了miR-150-5p水平，导致细胞凋亡增加和自噬减少。此外，MALAT1的过表达抑制了下游PI3K/Akt信号通路。用miR-150-5p模拟物恢复miR-150-5p水平可减少细胞凋亡并增加自噬，且下游PI3K/Akt信号通路被重新激活。
有氧运动通过抑制CHF中的lncRNA MALAT1改善心脏功能，其潜在机制可能通过miR-150-5p/PI3K/Akt信号通路介导。
