Comparative Effects of Acute and Chronic Resistance Training on Cardiac Angiogenesis: Insights into HIF-1 Dependent and Independent Mechanisms

Background: Angiogenesis is critical for cardiac function recovery and maintenance. Resistance training (RT) has been recognized as a potent stimulus for cardiovascular adaptation; however, its effect on cardiac angiogenesis remains unclear. Objectives: This study aimed to investigate the differential effects of acute versus chronic RT on cardiac angiogenesis regulators (HIF-1α, PGC-1α, FSTL 1, VEGF mRNA). Methods: 18-male Wistar rats (age: 10 weeks, body weight: 232.1 ± 5.04 g, heart weight: 0.96 ± 0.03 g) were randomly assigned to three groups: sedentary control (n=6), acute resistance training (ART) (n=6), and chronic resistance training (CRT) (n=6). The ART group underwent a single bout of RT, whereas the CRT group underwent RT for 8 weeks. Training was performed using a weighted climbing-up ladder with a progressive load tied to the tail of the rat. Left ventricular tissue was collected 1 h post-exercise to analyze HIF-1α, PGC-1α, VEGF, and FSTL1 mRNA expression by qRT-PCR. Results: ART significantly upregulated HIF-1α (0.78±0.03 vs 0.65±0.04), PGC-1α (0.15±0.02 vs 0.06±0.01), FSTL 1 (0.68±0.04 vs 0.30±0.08), and VEGF (0.26±0.01 vs 0.21±0.03) mRNA levels compared to the control group (p < 0.05), suggesting an early hypoxia-driven angiogenic response. Compared to the ART, the CRT group exhibited sustained elevations in PGC-1α (0.41±0.10), FSTL1 (0.93±0.15), and VEGF (0.32±0.02) mRNA (p < 0.05), indicating a shift toward HIF-1α-independent angiogenic pathways. These findings indicate that chronic exercise does not induce long-term hypoxia, which is suspected to be due to anti-HIF. However, VEGF expression remained high in the CRT group, reinforcing its role in long-term vascular adaptation, without involving the hypoxic pathway. Conclusion: Acute resistance training induces cardiac angiogenesis through a HIF-1α-dependent pathway, while chronic training engages a HIF-1α-independent mechanism via PGC-1α and FSTL1. These findings revealing distinct regulatory pathways and potential therapeutic targets for cardiovascular health.