Effects of exercise on ferroptosis and autophagy-related factors in cardiac tissue of angiotensin II-injected mice

초록

Background Angiotensin II (Ang II) is a main cause of cardiac remodeling from hypertension, will lead to inflammation, impaired autophagy, and ferroptosis. It is well established that exercise has cardioprotective benefits. However, it is not clear whether exercise alters ferroptosis and autophagy in Ang II-induced cardiac injury. Methods Twenty-four male C57BL/6 mice were randomly divided into four groups: control, Ang II, Ang II+low-intensity exercise (LIE), and Ang II+high-intensity exercise (HIE). Ang II was administered for 4 weeks, while the exercise groups performed treadmill exercise 5 days/week. Cardiac tissue was analyzed using hematoxylin-eosin staining, Western blotting, reverse transcription quantitative PCR, and correlation analysis. Results After 4 weeks of intervention, Ang II injection increased TNF-alpha and p62 protein levels (p < 0.05). Ang II+HIE significantly reduced TNF-alpha and IL-6 expression and restored autophagy markers (p < 0.05). Regarding ferroptosis, exercise did not change the NRF2 and GPX4 protein levels, but Gpx4 mRNA was elevated in the Ang II+LIE group. Pearson correlation analysis revealed that TNF-alpha was negatively correlated with NRF2/GPX4 and autophagy proteins, while NRF2 was positively correlated with ATG3/ATG7 and negatively correlated with p62. Conclusion The findings indicate that HIE had a greater influence on Ang II-induced cardiac inflammatory responses and autophagy-related markers. In contrast, LIE showed partial effects, including decreased p62 expression and increased Gpx4 mRNA expression. The changes in exercise-induced ferroptosis-related factors were mainly at the transcription level, not protein level. The results suggest that exercise intensity differentially modulates inflammation, autophagy-related markers, and ferroptosis-related responses in Ang II-induced cardiac stress.

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