GSTP1 inhibits angiotensin II-induced atrial fibrillation by regulating ferroptosis

Atrial fibrillation is the most common arrhythmia in clinical practice and increases the potential risk of stroke, thromboembolism, and death. Glutathione-S-transferases pi 1 (GSTP1), a key factor of ferroptosis, can participate in stress signal and cell damage pathway through its non-catalytic activity, and has the role of regulating and protecting cells from carcinogens and electrophilic compounds. However, the role and mechanism of GSTP1 in angiotensin II-induced atrial fibrillation have not been studied.

We constructed a mouse model of atrial fibrillation using Ang II and identified key factors by proteome and ferroptosis PCR array. We investigated the role of GSTP1 in atrial remodelling and NRAMs by the ferroptosis inhibitor Ferrostatin-1 (Fer-1), AAV9-cTNT-GSTP1, and GSTP1 inhibitor Ezatiostat. The results showed that the ferroptosis pathway was significantly altered in atrial fibrillation by proteomics. The ferroptosis inhibitor Fer-1 demonstrated that inhibiting ferroptosis can intervene in Ang II-induced atrial fibrillation. The ferroptosis PCR array showed that the expression of GSTP1 was significantly decreased in atrial fibrillation, and it was verified in cells and human atrial tissues. In mice infected with AAV9-cTNT-GSTP1, it was found that overexpression of GSTP1 inhibited Ang II-induced atrial fibrillation. Overexpression of GSTP1 inhibited Ang II-induced myocardial injury, oxidative stress, and ferroptosis in vitro.

Therefore, these results preliminarily demonstrate that GSTP1-mediated ferroptosis plays a crucial role in the Ang II-induced atrial fibrillation model and can be considered a potential therapeutic target for atrial fibrillation.