Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Third Hospital, Beijing, 100191, China.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
J Cardiovasc Transl Res. 2019 Dec;12(6):528-538. doi: 10.1007/s12265-019-09894-1. Epub 2019 Jun 3.
During acute sympathetic stress, the overactivation of β-adrenergic receptors (β-ARs) causes cardiac fibrosis by triggering inflammation and cytokine expression. It is unknown whether exercise training inhibits acute β-AR overactivation-induced cytokine expression and cardiac injury. Here, we report that running exercise inhibited cardiac fibrosis and improved cardiac function in mice treated with isoproterenol (ISO), a β-AR agonist. A cytokine antibody array revealed that running exercise prevented most of the changes in cytokine expression induced by ISO. Specifically, ISO-induced upregulation of 18 cytokines was prevented by running exercise. A Kyoto encyclopedia of genes and genomes analysis of these cytokines revealed that Hedgehog and RAP1 signaling pathways were involved in the regulation of cytokine expression by exercise. The changes in the expression of some cytokines that were prevented by exercise were verified by an enzyme-linked immunosorbent assay and real-time PCR. In conclusion, running exercise prevented the cytokine expression changes after acute β-AR overactivation and therefore attenuated cardiac fibrosis. Acute sympathetic stress is an important risk factor for the patients with cardiovascular diseases, and the present study revealed that exercise training can prevent against the upregulation of cytokines and the subsequent cardiac injury induced by acute sympathetic stress, suggesting that exercise training may be beneficial for cardiovascular patients who are in risk of acute sympathetic stress. This finding provides a theoretical basis for the application of exercise training in patients who may suffer from acute sympathetic stress.
在急性交感神经应激时，β-肾上腺素能受体（β-AR）的过度激活通过触发炎症和细胞因子表达导致心脏纤维化。目前尚不清楚运动训练是否抑制急性β-AR 过度激活诱导的细胞因子表达和心脏损伤。在这里，我们报告跑步运动抑制了异丙肾上腺素（ISO）处理的小鼠的心脏纤维化并改善了心脏功能，ISO 是一种β-AR 激动剂。细胞因子抗体阵列显示，跑步运动可预防 ISO 诱导的细胞因子表达的大多数变化。具体而言，跑步运动可预防 ISO 诱导的 18 种细胞因子的上调。对这些细胞因子的京都基因与基因组百科全书分析表明，Hedgehog 和 RAP1 信号通路参与了运动对细胞因子表达的调节。通过酶联免疫吸附测定和实时 PCR 验证了一些被运动预防的细胞因子表达变化。总之，跑步运动可预防急性β-AR 过度激活后细胞因子表达的变化，从而减轻心脏纤维化。急性交感神经应激是心血管疾病患者的一个重要危险因素，本研究表明，运动训练可以预防急性交感神经应激引起的细胞因子上调和随后的心脏损伤，这表明运动训练可能对处于急性交感神经应激风险中的心血管病患者有益。这一发现为可能遭受急性交感神经应激的患者应用运动训练提供了理论依据。
