Abstract
Ischemia-reperfusion (IR) injury commonly arises during cardiac surgery involving Cardiopulmonary Bypass (CPB), and it has relationship with ferroptosis in mice. However, the exact role of ferroptosis in the human cardiac damage caused by cardiac surgery remains unclear. Basic patient data and perioperative period information were collected, and clinic indicators related to cardiac function were detected to assess the extent of cardiac injury. Cardiac tissue samples were collected to determine histopathological changes, ultrastructure of mitochondrial and hallmarks of ferroptosis. 25 patients were involved in this study. In the present study, we observed a significant increase in the clinical indicator hs-cTnT, with levels rising more than 1393 ± 242 folds (P < 0.0001) following the cardiac surgery. Masson staining revealed a notable increase in fibrosis levels by 2.282 ± 0.259% (P = 0.0009). Furthermore, there was a significant elevation in lipid peroxidation, as evidenced by a 61.42 ± 17.33% increase in MDA (P = 0.0006). Additionally, we observed notable swelling, decreased mitochondrial crista, and even fragmented mitochondria. Notably, changes in the marker gene of ferroptosis were observed, with PTGS2 showing a 6.437 ± 0.81 folds increase (P < 0.0001). Furthermore, key regulators such as SLC7A11 and GPX4 proteins exhibited a reduction of 97.33 ± 25.78% (P = 0.0068) and 60.59 ± 14.93% (P = 0.0071), respectively, indicating the occurrence of ferroptosis following the surgery. Ferroptosis exists in myocardial IR injury caused by cardiac surgery with CPB, indicating that targeting ferroptosis could serve as a potential strategy for myocardial protection against CPB-induced IR injury. The trial has been registered in Chinese Clinical Trial Registry (ChiCTR, No. ChiCTR2200061995) on July 16th, 2022.
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Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 81903314); the Henan Provincial Science and Technology Research Project (Grant No. 232102310515); the Key Research Projects of Colleges and universities in Henan province (Grant NO. 24A330006).
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S.Z. contributed to the study conception and design. Material preparation and clinic data collection were performed by X.Z. The detection of the tissues and data analysis were performed by J.L. The first draft of the manuscript was written by J.L. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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This trial is approved by the First Affiliated Hospital of Zhengzhou University’s Ethics Committee (No. 2020-KY-0086) and has been successfully registered in the Chinese Clinical Trial Registry (ChiCTR, URL https://www.chictr.org.cn) with the registration number ChiCTR2200061995 on July 16th, 2022. This study adheres to the Helsinki Declaration.
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Zhang, S., Li, J., Wang, J. et al. Ferroptosis Exists in Ischemia Reperfusion Injury after Cardiac Surgery with Cardiopulmonary Bypass. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01228-6
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DOI: https://doi.org/10.1007/s12013-024-01228-6