Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents
This review explores ferroptosis, a form of regulated cell death reliant on iron-induced phospholipid peroxidation, in diverse physiological and pathological contexts, including neurodegenerative disorders, and ischemia-reperfusion. In the realm of cardiovascular diseases, it significantly contribut...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/558 |
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| author | John Dawi Scarlet Affa Edgar Gonzalez Yura Misakyan David Nikoghosyan Karim Hajjar Samuel Kades Sabrina Fardeheb Hayk Mirzoyan Vishwanath Venketaraman |
| author_facet | John Dawi Scarlet Affa Edgar Gonzalez Yura Misakyan David Nikoghosyan Karim Hajjar Samuel Kades Sabrina Fardeheb Hayk Mirzoyan Vishwanath Venketaraman |
| author_sort | John Dawi |
| collection | DOAJ |
| description | This review explores ferroptosis, a form of regulated cell death reliant on iron-induced phospholipid peroxidation, in diverse physiological and pathological contexts, including neurodegenerative disorders, and ischemia-reperfusion. In the realm of cardiovascular diseases, it significantly contributes to cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. Ferroptosis involves intricate interactions within cellular iron metabolism, lipid peroxidation, and the balance between polyunsaturated and monounsaturated fatty acids. Molecularly, factors like p53 and NRF2 impact cellular susceptibility to ferroptosis under oxidative stress. Understanding ferroptosis is vital in cardiomyopathies, where cardiac myocytes heavily depend on aerobic respiration, with iron playing a pivotal role. Dysregulation of the antioxidant enzyme GPX4 is linked to cardiomyopathies, emphasizing its significance. Ferroptosis’s role in myocardial ischemia-reperfusion injury, exacerbated in diabetes, underscores its relevance in cardiovascular conditions. This review explores the connection between ferroptosis, the NRF2 pathway, and atherosclerosis, emphasizing their roles in protecting cells from oxidative stress and maintaining iron balance. It discusses the use of iron chelating agents in managing iron overload conditions, with associated benefits and challenges. Finally, it highlights the importance of exploring therapeutic strategies that enhance the glutathione (GSH) system and the potential of natural compounds like quercetin, terpenoids, and phenolic acids in reducing oxidative stress. |
| first_indexed | 2024-04-24T18:31:06Z |
| format | Article |
| id | doaj.art-50af659512e040cab89ce13cfc941f7f |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:31:06Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-50af659512e040cab89ce13cfc941f7f2024-03-27T13:22:48ZengMDPI AGBiomedicines2227-90592024-03-0112355810.3390/biomedicines12030558Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating AgentsJohn Dawi0Scarlet Affa1Edgar Gonzalez2Yura Misakyan3David Nikoghosyan4Karim Hajjar5Samuel Kades6Sabrina Fardeheb7Hayk Mirzoyan8Vishwanath Venketaraman9College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USADepartment of Chemistry, Physics, and Engineering, Los Angeles Valley College, Valley Glen, CA 91401, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USACollege of Osteopathic Medicine, Touro University Nevada, Henderson, NV 89014, USACollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USAThis review explores ferroptosis, a form of regulated cell death reliant on iron-induced phospholipid peroxidation, in diverse physiological and pathological contexts, including neurodegenerative disorders, and ischemia-reperfusion. In the realm of cardiovascular diseases, it significantly contributes to cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. Ferroptosis involves intricate interactions within cellular iron metabolism, lipid peroxidation, and the balance between polyunsaturated and monounsaturated fatty acids. Molecularly, factors like p53 and NRF2 impact cellular susceptibility to ferroptosis under oxidative stress. Understanding ferroptosis is vital in cardiomyopathies, where cardiac myocytes heavily depend on aerobic respiration, with iron playing a pivotal role. Dysregulation of the antioxidant enzyme GPX4 is linked to cardiomyopathies, emphasizing its significance. Ferroptosis’s role in myocardial ischemia-reperfusion injury, exacerbated in diabetes, underscores its relevance in cardiovascular conditions. This review explores the connection between ferroptosis, the NRF2 pathway, and atherosclerosis, emphasizing their roles in protecting cells from oxidative stress and maintaining iron balance. It discusses the use of iron chelating agents in managing iron overload conditions, with associated benefits and challenges. Finally, it highlights the importance of exploring therapeutic strategies that enhance the glutathione (GSH) system and the potential of natural compounds like quercetin, terpenoids, and phenolic acids in reducing oxidative stress.https://www.mdpi.com/2227-9059/12/3/558ferroptosisGPX4NRF2GSHoxidative stresscardiomyopathy |
| spellingShingle | John Dawi Scarlet Affa Edgar Gonzalez Yura Misakyan David Nikoghosyan Karim Hajjar Samuel Kades Sabrina Fardeheb Hayk Mirzoyan Vishwanath Venketaraman Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents Biomedicines ferroptosis GPX4 NRF2 GSH oxidative stress cardiomyopathy |
| title | Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents |
| title_full | Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents |
| title_fullStr | Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents |
| title_full_unstemmed | Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents |
| title_short | Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents |
| title_sort | ferroptosis in cardiovascular disease and cardiomyopathies therapeutic implications of glutathione and iron chelating agents |
| topic | ferroptosis GPX4 NRF2 GSH oxidative stress cardiomyopathy |
| url | https://www.mdpi.com/2227-9059/12/3/558 |
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