Background: Regular physical activity (PA) and structured exercise are linked to reduced incidence and mortality of cardiovascular disease (CVD). Therefore, current guidelines recommend engaging in at least 150 minutes of moderate‑intensity or 75 minutes of vigorous‑intensity PA per week (or equivalent combinations). Nevertheless, approximately one-third of the global population fails to meet these recommendations.
From a pathophysiological standpoint, a sedentary lifestyle contributes to chronic, low-grade systemic inflammation, which in turn significantly accelerates the onset and progression of chronic inflammatory diseases of the vessel wall, ultimately leading to atherosclerosis. Myocardial infarction (MI), a severe complication of atherosclerotic disease, triggers a strong systemic inflammatory response that recruits numerous leukocytes into the ischemic myocardium. Persistent inflammation following MI has been shown to be associated with impaired wound healing, adverse remodelling, and heart failure.
Methods and Results: To investigate the role of prior physical activity on persistent inflammation, we utilized cages equipped with a running wheel, enabling voluntary running, while “sedentary” control mice (SED) were housed in equivalent cages without a running wheel. After 6 weeks of voluntary running, we analysed the blood leukocytes using flow cytometry. Notably, we observed a significant and robust reduction in circulating blood leukocytes in physically active mice compared to the sedentary control cohort (live leukocytes/μl: 6621±3197 in PA, 9073±3787 in SED, p=0.0298). This effect was observed in both male and female C57BL/6 wildtype mice, consistent with previously published evidence in humans. We then performed ligation of the left anterior descending artery (LAD) to induce MI in mice either housed in cages equipped with a running wheel or without. 72 hours after MI, we analysed immune cell composition in the ischemic area by flow cytometry. Here, we observed a significant reduction in leukocytes recruited into the infarcted myocardium of physically active mice compared to sedentary control mice (live leukocytes/mg: 30.2x103 ± 11.1x103 in PA, 42.8x103 ± 16.2x103 in SED, p=0.0027). Prolonged inflammation following MI is linked to impaired wound healing, adverse remodelling, and, ultimately, heart failure. Thus, we investigated the effect of prior habitual physical activity on functional recovery following MI. Physically active and sedentary ApoE-/- mice on a high-cholesterol diet were subjected to LAD ligation, and left ventricular function was assessed 4 weeks post-MI using echocardiography. Indeed, we observed a better-preserved left ventricular ejection fraction (LV-EF) in physically active mice compared to sedentary controls (EF: 45.1 ± 5.6% in PA, 32.9 ± 9.1% in SED, p=0.0022), thus indicating improved functional infarct healing.
Conclusion: This study demonstrates that prior physical activity reduces blood leukocyte count in mice. Following LAD-ligation-induced MI, physical activity is associated with lower immune cell infiltration in ischemic areas, which leads to improved functional infarct healing. Thus, physical activity may be harnessed as a potential anti-inflammatory therapy concept in CVD.
