Sun Yulin, Liu Yining
Department of Sports Science, Hanyang University ERICA, Ansan 15588, Republic of Korea.
Int J Mol Sci. 2025 May 12;26(10):4615. doi: 10.3390/ijms26104615.
Cardiovascular diseases (CVDs) represent a major public health concern globally, being one of the leading causes of illness and death across populations. While physical activity is widely recognized as a protective factor against these diseases, the exact biological mechanisms that explain this relationship are still not fully understood. This study utilized a two-sample Mendelian randomization (MR) method to investigate the potential role of circulating cytokines in mediating the effects of physical activity on major CVD outcomes, including coronary artery disease (CAD), heart failure (HF), and ischemic heart disease (IHD). Our primary MR analysis revealed an inverse association between physical activity and IHD risk. Moreover, a two-step MR mediation approach identified IL10RB (Interleukin-10 receptor subunit beta) as an intermediate mediator, explaining about 6.65% of the observed contribution of physical activity to IHD. These results indicate that physical activity may mitigate CVD risk through modulation of immune pathways, particularly via IL10RB signaling. Our findings underscore the significance of cytokine networks in mediating the cardiovascular benefits of exercise and suggest potential therapeutic strategies for CVD risk reduction through immune system modulation.
心血管疾病（CVDs）是全球主要的公共卫生问题，是不同人群患病和死亡的主要原因之一。虽然体育活动被广泛认为是预防这些疾病的保护因素，但解释这种关系的确切生物学机制仍未完全明确。本研究采用两样本孟德尔随机化（MR）方法，调查循环细胞因子在介导体育活动对主要心血管疾病结局（包括冠状动脉疾病（CAD）、心力衰竭（HF）和缺血性心脏病（IHD））影响中的潜在作用。我们的主要MR分析揭示了体育活动与IHD风险之间存在负相关。此外，两步MR中介方法确定白细胞介素10受体亚基β（IL10RB）为中间介质，解释了体育活动对IHD观察到的贡献的约6.65%。这些结果表明，体育活动可能通过调节免疫途径，特别是通过IL10RB信号传导来降低心血管疾病风险。我们的研究结果强调了细胞因子网络在介导运动对心血管益处中的重要性，并提出了通过调节免疫系统降低心血管疾病风险的潜在治疗策略。
