Differential Effect of Acute and Chronic Exercise on Cardiac Angiogenesis Regulator: The Role of mRNA HIF-1α and Its Negative Regulators of In Vivo Study.

Introduction: Angiogenesis is a critical adaptation to regular physical exercise, primarily driven by hypoxia-inducible factor-1 alpha (HIF-1α). However, prolonged exercise has been associated with the downregulation of HIF-1α, potentially mediated by increased expression of its negative regulators, prolyl hydroxylase domain (PHD) and factor-inhibiting HIF-1 (FIH). Objectives: This study aimed to investigate the effects of short-term (acute) and long-term (chronic) moderate-intensity exercise on HIF-1α, PHD, and FIH mRNA expression in Wistar rat hearts. Methods: Twenty Wistar rats (age: 8 weeks, body weight: 200-250 g) were divided into four groups: acute control (AC) (15 days) (n = 5), acute exercise (AE) (15 days) (n = 5), chronic control (CC) (8 weeks) (n = 5), and chronic exercise (CE) (8 weeks) (n = 5). The exercise groups underwent moderate-intensity treadmill exercise with 20 m/min for 30 min each day for 5 times a week. At the end of the experiment, rats were sacrificed 1 h (acute group) and 24 h (chronic group) after exercise using isoflurane anesthesia, followed by cervical dislocation. Left ventricular heart muscle samples were collected for mRNA expression analysis of HIF-1α, PHD, and FIH using real-time PCR. Results: Exercise significantly altered the expression of HIF-1α, PHD, and FIH. HIF-1α mRNA was significantly higher in the AE group versus AC (AC vs AE, p=0.006) and in the CE group versus CC (CC vs CE, p=0.004). PHD expression likewise increased with exercise (AE vs AC, p=0.001; CE vs CC, p ≤ 0.001). In contrast, FIH showed no significant differences (acute p=0.472; chronic p=0.095). Exploratory one-way analyses confirmed overall group effects for HIF-1α (p ≤ 0.001) and PHD (p=0.016), but not for FIH (p=0.105). Conclusion: Chronic moderate-intensity exercise upregulates the expression of HIF-1α negative regulators (PHD and FIH) in the myocardium, suggesting a shift from acute hypoxia-driven responses to oxygen-dependent regulation. These findings offer insight into the molecular adaptations of cardiac tissue to prolonged exercise and their potential role in angiogenesis regulation.