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Review
. 2024 Jan 11;25(2):897.
doi: 10.3390/ijms25020897.

Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury

Vyacheslav V Ryabov  1 , Leonid N Maslov  1 , Evgeniy V Vyshlov  1 , Alexander V Mukhomedzyanov  1 , Mikhail Kilin  1 , Svetlana V Gusakova  2 , Alexandra E Gombozhapova  1 , Oleg O Panteleev  1
Affiliations
Review

Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury

Vyacheslav V Ryabov et al. Int J Mol Sci. .

Abstract

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased in recent years. The leading cause of death of these patients is ischemia/reperfusion (I/R) cardiac injury. It is quite obvious that there is an urgent need to create new drugs for the treatment of STEMI based on knowledge about the pathogenesis of I/R cardiac injury, in particular, based on knowledge about the molecular mechanism of ferroptosis. In this study, it was demonstrated that ferroptosis is involved in the development of I/R cardiac injury, antitumor drug-induced cardiomyopathy, diabetic cardiomyopathy, septic cardiomyopathy, and inflammation. There is indirect evidence that ferroptosis participates in stress-induced cardiac injury. The activation of AMPK, PKC, ERK1/2, PI3K, and Akt prevents myocardial ferroptosis. The inhibition of HO-1 alleviates myocardial ferroptosis. The roles of GSK-3β and NOS in the regulation of ferroptosis require further study. The stimulation of Nrf2, STAT3 prevents ferroptosis. The activation of TLR4 and NF-κB promotes ferroptosis of cardiomyocytes. MiR-450b-5p and miR-210-3p can increase the tolerance of cardiomyocytes to hypoxia/reoxygenation through the inhibition of ferroptosis. Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p and miR-15a-5p can aggravate myocardial ferroptosis.

Keywords: cardiomyopathy; ferroptosis; heart; ischemia/reperfusion; kinases; microRNAs.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The role of kinases and transcription factors in the regulation of ferroptosis. Red arrows are inhibitors of ferroptosis, and green arrows are inducers of ferroptosis.
Figure 2
Figure 2
The role of non-coding RNAs in the regulation of ferroptosis. Perpendicular arrows are inhibitors of ferroptosis, arrows are inducers of ferroptosis.
Figure 3
Figure 3
Factors inhibiting ferroptosis. Perpendicular arrows are inhibition of ferroptosis.
Figure 4
Figure 4
Factors stimulating ferroptosis. Arrows are stimulation of ferroptosis.
Figure 5
Figure 5
The involvement of ferroptosis in cardiovascular pathologies. Black arrows are stimulation of processes, red and yellow arrows are inhibition of processes.
See this image and copyright information in PMC

References

    1. Menees D.S., Peterson E.D., Wang Y., Curtis J.P., Messenger J.C., Rumsfeld J.S., Gurm H.S. Door-to-Balloon Time and Mortality among Patients Undergoing Primary PCI. N. Engl. J. Med. 2013;369:901–909. doi: 10.1056/NEJMoa1208200. - DOI - PubMed
    1. Fabris E., Kilic S., Schellings D.A.A.M., Ten Berg J.M., Kennedy M.W., van Houwelingen K.G., Giannitsis E., Kolkman E., Ottervanger J.P., Hamm C., et al. Long-Term Mortality and Prehospital Tirofiban Treatment in Patients with ST Elevation Myocardial Infarction. Heart. 2017;103:1515–1520. doi: 10.1136/heartjnl-2017-311181. - DOI - PubMed
    1. Vaidya S.R., Devarapally S.R., Arora S. Infarct Related Artery Only versus Complete Revascularization in ST-Segment Elevation Myocardial Infarction and Multi Vessel Disease: A Meta-Analysis. Cardiovasc. Diagn. Ther. 2017;7:16. doi: 10.21037/cdt.2016.08.06. - DOI - PMC - PubMed
    1. Olier I., Sirker A., Hildick-Smith D.J.R., Kinnaird T., Ludman P., De Belder M.A., Baumbach A., Byrne J., Rashid M., Curzen N., et al. Association of Different Antiplatelet Therapies with Mortality after Primary Percutaneous Coronary Intervention. Heart. 2018;104:1683–1690. doi: 10.1136/heartjnl-2017-312366. - DOI - PubMed
    1. Megaly M., Pershad A., Glogoza M., Elbadawi A., Omer M., Saad M., Mentias A., Elgendy I., Burke M.N., Capodanno D. Use of Intravascular Imaging in Patients with ST-Segment Elevation Acute Myocardial Infarction. Cardiovasc. Revasc. Med. 2021;30:59–64. doi: 10.1016/j.carrev.2020.09.032. - DOI - PubMed