Molecular Mechanisms of Exercise-Induced Cardioprotection in Adults with Hypertensive Heart Disease: A Randomised Interventional Study in Abuja

Exercise training confers cardioprotection in hypertensive heart disease through molecular mechanisms including nitric oxide bioavailability, oxidative stress reduction, and myocardial autophagy regulation, yet these pathways have not been characterised in a Nigerian clinical interventional trial. This study investigated the molecular mechanisms underlying exercise-induced cardioprotection in adults with hypertensive heart disease in Abuja, North Central Nigeria. A randomised controlled trial enrolled 90 patients with confirmed hypertensive heart disease assigned to either a twelve-week supervised moderate-intensity aerobic training programme or a standard care control group. Primary molecular endpoints measured from peripheral blood and platelet preparations included plasma nitric oxide metabolites, superoxide dismutase, glutathione peroxidase, malondialdehyde, circulating microRNA-21 as a cardiac remodelling marker, and galectin-3 as a fibrosis indicator. Echocardiographic indices of left ventricular structure and function were assessed at baseline and post-intervention. Mixed ANOVA, mediation analysis, and bioinformatic pathway enrichment were applied. Results showed significant increases in nitric oxide metabolites, superoxide dismutase, and glutathione peroxidase in the exercise group, alongside reductions in malondialdehyde, galectin-3, and circulating microRNA-21. Left ventricular mass index was significantly reduced in exercised patients. Nitric oxide upregulation mediated 40 percent of the left ventricular mass reduction. This study provides novel molecular mechanistic evidence for exercise cardioprotection in hypertensive heart disease in Nigeria, advancing translational physiology. Molecular biomarker-guided exercise prescription is proposed for cardiac rehabilitation frameworks. Keywords: cardioprotection, exercise, nitric oxide, hypertensive heart disease, Abuja.