Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Lai-Hua Xie
 -- 1501 2022-09-06 16:22:26 |
2 format correct
Catherine Yang
 Meta information modification 1501 2022-09-07 04:48:14 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Xie, L.;  Fefelova, N.;  Pamarthi, S.H.;  Gwathmey, J.K. Implications of Ferroptosis in Cardiovascular Disease. Encyclopedia. Available online: https://encyclopedia.pub/entry/26925 (accessed on 18 November 2024).
Xie L,  Fefelova N,  Pamarthi SH,  Gwathmey JK. Implications of Ferroptosis in Cardiovascular Disease. Encyclopedia. Available at: https://encyclopedia.pub/entry/26925. Accessed November 18, 2024.
Xie, Lai-Hua, Nadezhda Fefelova, Sri Harika Pamarthi, Judith K. Gwathmey. "Implications of Ferroptosis in Cardiovascular Disease" Encyclopedia, https://encyclopedia.pub/entry/26925 (accessed November 18, 2024).
Xie, L.,  Fefelova, N.,  Pamarthi, S.H., & Gwathmey, J.K. (2022, September 06). Implications of Ferroptosis in Cardiovascular Disease. In Encyclopedia. https://encyclopedia.pub/entry/26925
Xie, Lai-Hua, et al. "Implications of Ferroptosis in Cardiovascular Disease." Encyclopedia. Web. 06 September, 2022.
Implications of Ferroptosis in Cardiovascular Disease
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cells11172726

Ferroptosis has recently been demonstrated to be a novel regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation that results in membrane damage. Ferroptosis plays an essential role in the development of diverse cardiovascular diseases (CVDs), such as hemochromatosis-associated cardiomyopathy, doxorubicin-induced cardiotoxicity, ischemia/reperfusion (I/R) injury, heart failure (HF), atherosclerosis, and COVID-19–related arrhythmias.

ferroptosis cardiovascular disease iron ROS

1. Hemochromatosis-Associated Cardiomyopathy

While iron is required for normal physiological processes, it can become toxic when iron overload occurs, such as in patients with hereditary forms of hemochromatosis or as a result of multiple blood transfusions as seen with sickle cell disease or in patients with β-thalassemia [1]. The heart is one of the major target organs for iron deposition which can be manifested as iron overload cardiomyopathy (IOC) [2][3]. IOC is the leading cause of morbidity and mortality in patients with primary hemochromatosis and secondary iron overload. These patients exhibit cardiomyopathy as well as life-threatening cardiac arrhythmias. Although IOC remains a global tragedy and significant clinical challenge in the U.S. and internationally, the underlying mechanism(s) involved in IOC iron-associated cardiotoxicity have not been well defined [1][3][4].
Ferroptosis has recently been implicated in iron overload-induced cardiac cell death and cardiovascular disease [5][6][7][8]. Baba et al. have demonstrated that ferric iron-citrate, erastin, and RSL3 readily induce ferroptosis in cultured adult mouse cardiomyocytes, which can be reversed by the ferroptosis inhibitor ferrostatin-1 [5]. Iron catalyzes the Fenton reaction, resulting in the formation of soluble peroxides or lipid peroxides that then generate toxic hydroxyl or lipid alkoxyl radicals, which can then propagate lipid peroxidation. Baba et al. further demonstrated that the mechanistic target of rapamycin (mTOR) plays an important role in protecting cardiomyocytes against excess iron and ferroptosis, probably by regulating ROS production [5].
It is well known that mitochondria play an important role in the process of iron metabolism. Iron overload may occur at the cellular as well as mitochondrial level. It should be noted that mitochondrial iron overload may play an important role in causing mitochondrial dysfunction and even ferroptosis [1][9][10][11]. Iron overload promotes ROS production, depolarizes mitochondrial membrane potential (ΔΨm), and disrupts cytosolic Ca dynamics. Cytosolic Ca dysregulation is a recognized hallmark of cardiac dysfunction and heart failure [12]. The involvement of the mitochondrial permeability transition pore (mPTP) has been suggested as contributing to cytosolic Ca dysregulation [13]. Kumfu et al. have shown that mCU is involved in mitochondrial dysfunction under iron-loaded conditions [10]. Iron overload-induced ferroptosis is dependent on the mitochondrial Ca uniporter (mCU) using a conditional mCU KO mouse model created by Kwong et al. [14]. Supporting the importance of mitochondrial labile iron in the induction of ferroptosis, it has also been reported that overexpression of the iron-storage protein ferritin in mitochondria suppresses erastin-induced ferroptosis [15]. However, detailed mechanisms for mitochondrial iron metabolism in the regulation of mitochondrial (dys)function and ferroptosis, such as the role of mCU, crosstalk between Ca and iron, compartmentalization of lipid peroxides, etc., are still not well understood. Nevertheless, preventing cellular and mitochondrial iron overload by either reducing iron uptake or increasing iron storage, e.g., via transferrin, may inhibit the occurrence of ferroptosis. Iron chelators have also been widely used to treat IOC [1].

2. Cardio-Oncology: Doxorubicin-Induced Cardiomyopathy

Doxorubicin (DOX) is a widely used anthracycline anticancer agent. However, its clinical efficacy is limited by cardiotoxicity referred to as doxorubicin-induced cardiomyopathy (DIC). The detailed mechanisms for DIC and its therapeutic strategy have yet to be fully elucidated. Previous studies have linked Ca handling abnormalities, mitochondrial iron accumulation, and mitochondrial dysfunction to DIC [16][17][18][19]. It has also been suggested that several RCDs such as apoptosis, necroptosis, and autophagy are involved in DOX-induced cardiomyocyte death [16][17][20][21][22]. Several recent studies have recently demonstrated that ferroptosis is likely to be the major form of RCD in DOX-induced cardiomyocyte death. Therefore, therapeutics targeting ferroptosis might be a novel preventive strategy for DIC [23][24][25][26][27]. It has been demonstrated that heme oxygenase 1 (Hmox1)-dependent heme degradation and free iron overload promote ferroptosis and DIC [23]. Furthermore, doxorubicin has been shown to suppress mGPX4 expression thereby inducing excessive lipid peroxidation in mitochondria and might consequently lead to mitochondria-dependent ferroptosis. Furthermore, the overexpression of mGPX4 or iron chelation targeting mitochondrial iron content significantly rescued doxorubicin-induced ferroptosis [24]. Whether doxorubicin also suppresses the expression or activity of DHODH, another arm of the mitochondrial lipid peroxidation defense system, remains to be studied.

3. Cardiac Ischemia/Reperfusion (I/R) Injury

It has been observed that myocardial injury may lead to the release and accumulation of local iron [28]. Previous studies have suggested that mitochondrial iron is involved in cardiac ischemic events [29]. Iron regulatory proteins such as transferrin receptor 1 [30] and ferroportin [31] have been shown to be associated with myocardial I/R injury. Furthermore, the overexpression of GPX4 in mitochondria suppresses I/R injury and reduces lipid peroxidation [32], suggesting a potential association to ferroptosis. A number of very recent studies have further revealed cardiac I/R injury may cause the disruption (expression and activation) of the GPX4 system as well as trigger the accumulation of lipid peroxidation (such as oxidized phosphatidylcholines), thereby inducing cardiomyocyte ferroptosis [23][33][34][35][36][37]. In addition, the level of NOX2 (thus generation of ROS) has been shown to also be increased during myocardial I/R injury [38]. Moreover, it has been demonstrated that the Nrf2 pathway contributes to ferroptosis in I/R injury [39]. Administration of Fer-1 reduced infarct size caused by I/R injury and showed a long-term improvement in cardiac function [40]. Therefore, ferroptosis is associated with cardiac I/R injury as a significant form of cell death in cardiomyocytes, although it should be noted that apoptosis and necroptosis have also been observed in I/R injury.

4. Heart Failure

Heart failure (HF) is a serious condition characterized by significantly reduced cardiac output and cardiomyocyte cell death [12]. Recent studies have linked ferroptosis to HF induced by genetic manipulation in addition to receiving a diet high in iron content and the presence of pressure overload. Fang et al. [41] has demonstrated that the iron storage protein ferritin H (Fth) plays a central role in mediating cardiac iron homeostasis and protecting against cardiac ferroptosis and subsequent cardiomyopathy (even HF) induced by a diet with a high iron content. Fth-deficient mice showed increased ROS production and developed HF at 6 months of age with a high-iron diet. HF could have been ameliorated by either Fer-1 or by overexpression of xc− (SLC7A11), which increased GSH levels and suppressed ferroptosis. Furthermore, ferroptosis was found to play an important role in a rat HF model induced by transverse aortic constriction (TAC) [42]. Knocking-down Toll-like receptor 4 (TLR4) or NOX4 remarkably reduced the incidence of ferroptosis and improved heart function, suggesting that TLR4-NOX4 might be a potential therapeutic target for HF at least partly through inhibiting ferroptosis-mediated cell death. Moreover, in a TAC-induced rat HF model, Liu et al. [43] suggested that puerarin, an isoflavone, may protect against HF induced by pressure overload by decreasing lipid peroxidation and mitigating ferroptosis.

5. Atherosclerosis

Atherosclerosis is a chronic inflammatory disease of arteries characterized by disorders of lipid metabolism. It has been previously realized that GPX4 and lipid peroxidation play significant roles in atherosclerosis. For example, Guo et al. [44] demonstrated that overexpression of GPX4 decreased lipid peroxidation and alleviated atherosclerotic lesions in the aorta of ApoE-deficient mice. Considering that reduced GPX4 expression and/or activation and increased lipid peroxidation are the main features of ferroptosis, recent studies [45] have explored the potential association between ferroptosis and atherosclerosis.
Bai et al. found that Fer-1 partially reduced iron accumulation, lipid peroxidation, and reversed the expressions of SLC7A11 and GPX4 in aortic endothelial cells in high fat diet-fed ApoE(−/−) mice [45]. Fer-1 reduced high fat diet-induced atherosclerotic lesions in ApoE-deficient mice by reducing lipid peroxidation. Furthermore, oxidized-low density lipoprotein (ox-LDL)-induced cell death was also examined in mouse aortic endothelial cells (in vitro). More importantly, Fer-1 reduced cell death in ox-LDL-treated cells, suggesting the involvement of ferroptosis during the initiation and development of atherosclerosis. In addition, ferroptosis has also been linked to atherosclerosis in human coronary artery specimens by analyzing the correlation to ferroptosis markers such as PTGS2 (upregulated), ACSL4 (upregulated), and GPX4 (downregulated) [46].

6. COVID-19 Associated Arrhythmias

Both excessive ROS generation and iron overload have a close association with arrhythmogenesis [1][13][47][48]. However, the implication of ferroptosis in arrhythmogenesis has not been investigated. It has been suggested that cardiac arrhythmias are one of the clinical features of coronavirus disease 2019 (COVID-19). An earlier study by Jacobs et al. observed lipid peroxidation in the myocardium and suggested that ferroptosis may be a detrimental factor in cardiac damage resulting from COVID-19 [49]. A recent study [50] investigated the potential role of ferroptosis-induced sinus node damage in causing cardiac arrhythmias. The study used human embryonic stem cell (hESC)-derived sinoatrial node (SAN)-like pacemaker cells and showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induced ferroptosis and caused the dysfunction of human SAN-like pacemaker cells. This result suggests that ferroptosis is a potential mechanism for inducing arrhythmias in patients with COVID-19. Iron chelators and/or ferroptosis inhibitors might be able to block SARS-CoV-2 infection and be used to treat cardiac arrhythmias as well as other CoV-2–associated organ failures.

References

  1. Gordan, R.; Wongjaikam, S.; Gwathmey, J.K.; Chattipakorn, N.; Chattipakorn, S.C.; Xie, L.-H. Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: An update. Heart Fail. Rev. 2018, 23, 801–816.
  2. Gujja, P.; Rosing, D.R.; Tripodi, D.J.; Shizukuda, Y. Iron Overload Cardiomyopathy: Better Understanding of an Increasing Disorder. J. Am. Coll. Cardiol. 2010, 56, 1001–1012.
  3. Kremastinos, D.T.; Farmakis, D. Iron Overload Cardiomyopathy in Clinical Practice. Circulation 2011, 124, 2253–2263.
  4. Murphy, C.J.; Oudit, G.Y. Iron-Overload Cardiomyopathy: Pathophysiology, Diagnosis, and Treatment. J. Card. Fail. 2010, 16, 888–900.
  5. Baba, Y.; Higa, J.K.; Shimada, B.K.; Horiuchi, K.M.; Suhara, T.; Kobayashi, M.; Woo, J.D.; Aoyagi, H.; Marh, K.S.; Kitaoka, H.; et al. Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am. J. Physiol. Circ. Physiol. 2018, 314, H659–H668.
  6. Doll, S.; Conrad, M. Iron and ferroptosis: A still ill-defined liaison. IUBMB Life 2017, 69, 423–434.
  7. Kobayashi, M.; Suhara, T.; Baba, Y.; Kawasaki, N.K.; Higa, J.K.; Matsui, T. Pathological Roles of Iron in Cardiovascular Disease. Curr. Drug Targets 2018, 19, 1068–1076.
  8. Ravingerová, T.; Kindernay, L.; Barteková, M.; Ferko, M.; Adameová, A.; Zohdi, V.; Bernátová, I.; Ferenczyová, K.; Lazou, A. The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection. Int. J. Mol. Sci. 2020, 21, 7889.
  9. Fefelova, N.; Wongjaikam, S.; Siri-Angkul, N.; Gwathmey, J.; Chattipakorn, N.; Chattipakorn, S.; Xie, L.-H. Abstract 15737: Deficiency of Mitochondrial Calcium Uniporter Protects Mouse Hearts From Iron Overload by Attenuating Ferroptosis. Circulation 2020, 142, A15737.
  10. Kumfu, S.; Chattipakorn, S.; Fucharoen, S.; Chattipakorn, N. Mitochondrial calcium uniporter blocker prevents cardiac mitochondrial dysfunction induced by iron overload in thalassemic mice. BioMetals 2012, 25, 1167–1175.
  11. Otasevic, V.; Vucetic, M.; Grigorov, I.; Martinovic, V.; Stancic, A. Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria. Oxidative Med. Cell. Longev. 2021, 2021, 5537330.
  12. Siri-Angkul, N.; Dadfar, B.; Jaleel, R.; Naushad, J.; Parambathazhath, J.; Doye, A.; Xie, L.-H.; Gwathmey, J. Calcium and Heart Failure: How Did We Get Here and Where Are We Going? Int. J. Mol. Sci. 2021, 22, 7392.
  13. Gordan, R.; Fefelova, N.; Gwathmey, J.K.; Xie, L.-H. Iron Overload, Oxidative Stress and Calcium Mishandling in Cardiomyocytes: Role of the Mitochondrial Permeability Transition Pore. Antioxidants 2020, 9, 758.
  14. Kwong, J.Q.; Lu, X.; Correll, R.N.; Schwanekamp, J.A.; Vagnozzi, R.J.; Sargent, M.A.; York, A.J.; Zhang, J.; Bers, D.M.; Molkentin, J.D. The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart. Cell Rep. 2015, 12, 15–22.
  15. Wang, Y.-Q.; Chang, S.-Y.; Wu, Q.; Gou, Y.-J.; Jia, L.; Cui, Y.-M.; Yu, P.; Shi, Z.-H.; Wu, W.-S.; Gao, G.; et al. The Protective Role of Mitochondrial Ferritin on Erastin-Induced Ferroptosis. Front. Aging Neurosci. 2016, 8, 308.
  16. Octavia, Y.; Tocchetti, C.G.; Gabrielson, K.L.; Janssens, S.; Crijns, H.J.; Moens, A.L. Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies. J. Mol. Cell. Cardiol. 2012, 52, 1213–1225.
  17. Zhang, T.; Zhang, Y.; Cui, M.; Jin, L.; Wang, Y.; Lv, F.; Liu, Y.; Zheng, W.; Shang, H.; Zhang, J.; et al. CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis. Nat. Med. 2016, 22, 175–182.
  18. Zhang, S.; Liu, X.; Bawa-Khalfe, T.; Lu, L.-S.; Lyu, Y.L.; Liu, L.F.; Yeh, E.T.H. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med. 2012, 18, 1639–1642.
  19. Ichikawa, Y.; Ghanefar, M.; Bayeva, M.; Wu, R.; Khechaduri, A.; Prasad, S.V.N.; Mutharasan, R.K.; Naik, T.J.; Ardehali, H. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J. Clin. Investig. 2014, 124, 617–630.
  20. Abdelwahid, E.; Wei, L. Apoptosis in Anthracycline Cardiomyopathy. Curr. Pediatr. Rev. 2011, 7, 329–336.
  21. Dirks-Naylor, A.J. The role of autophagy in doxorubicin-induced cardiotoxicity. Life Sci. 2013, 93, 913–916.
  22. Kitakata, H.; Endo, J.; Ikura, H.; Moriyama, H.; Shirakawa, K.; Katsumata, Y.; Sano, M. Therapeutic Targets for DOX-Induced Cardiomyopathy: Role of Apoptosis vs. Ferroptosis. Int. J. Mol. Sci. 2022, 23, 1414.
  23. Fang, X.; Wang, H.; Han, D.; Xie, E.; Yang, X.; Wei, J.; Gu, S.; Gao, F.; Zhu, N.; Yin, X.; et al. Ferroptosis as a target for protection against cardiomyopathy. Proc. Natl. Acad. Sci. USA 2019, 116, 2672–2680.
  24. Tadokoro, T.; Ikeda, M.; Ide, T.; Deguchi, H.; Ikeda, S.; Okabe, K.; Ishikita, A.; Matsushima, S.; Koumura, T.; Yamada, K.-I.; et al. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight 2020, 5.
  25. Kitakata, H.; Endo, J.; Matsushima, H.; Yamamoto, S.; Ikura, H.; Hirai, A.; Koh, S.; Ichihara, G.; Hiraide, T.; Moriyama, H.; et al. MITOL/MARCH5 determines the susceptibility of cardiomyocytes to doxorubicin-induced ferroptosis by regulating GSH homeostasis. J. Mol. Cell. Cardiol. 2021, 161, 116–129.
  26. Christidi, E.; Brunham, L.R. Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death Dis. 2021, 12, 1–15.
  27. Koleini, N.; Nickel, B.E.; Edel, A.L.; Fandrich, R.R.; Ravandi, A.; Kardami, E. Oxidized phospholipids in Doxorubicin-induced cardiotoxicity. Chem. Interact. 2019, 303, 35–39.
  28. Zykova, S.N.; Jenssen, T.G.; Berdal, M.; Olsen, R.; Myklebust, R.; Seljelid, R. Altered cytokine and nitric oxide secretion in vitro by macrophages from diabetic type II-like db/db mice. Diabetes 2000, 49, 1451–1458.
  29. Chang, H.-C.; Wu, R.; Shang, M.; Sato, T.; Chen, C.; Shapiro, J.S.; Liu, T.; Thakur, A.; Sawicki, K.T.; Prasad, S.V.N.; et al. Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol. Med. 2016, 8, 247–267.
  30. Tang, L.-J.; Zhou, Y.-J.; Xiong, X.-M.; Li, N.-S.; Zhang, J.-J.; Luo, X.-J.; Peng, J. Ubiquitin-specific protease 7 promotes ferroptosis via activation of the p53/TfR1 pathway in the rat hearts after ischemia/reperfusion. Free Radic. Biol. Med. 2020, 162, 339–352.
  31. Nishizawa, H.; Matsumoto, M.; Shindo, T.; Saigusa, D.; Kato, H.; Suzuki, K.; Sato, M.; Ishii, Y.; Shimokawa, H.; Igarashi, K. Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1. J. Biol. Chem. 2020, 295, 69–82.
  32. Dabkowski, E.R.; Williamson, C.L.; Hollander, J.M. Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction. Free Radic. Biol. Med. 2008, 45, 855–865.
  33. Komai, K.; Kawasaki, N.K.; Higa, J.K.; Matsui, T. The Role of Ferroptosis in Adverse Left Ventricular Remodeling Following Acute Myocardial Infarction. Cells 2022, 11, 1399.
  34. Stamenkovic, A.; O’Hara, K.A.; Nelson, D.C.; Maddaford, T.G.; Edel, A.L.; Maddaford, G.; Dibrov, E.; Aghanoori, M.; Kirshenbaum, L.A.; Fernyhough, P.; et al. Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia-reperfusion injury. Am. J. Physiol. Circ. Physiol. 2021, 320, H1170–H1184.
  35. Ying, H.; Shen, Z.; Wang, J.; Zhou, B. Role of iron homeostasis in the heart: Heart failure, cardiomyopathy, and ischemia-reperfusion injury. Herz 2021, 47, 141–149.
  36. Yeang, C.; Hasanally, D.; Que, X.; Hung, M.-Y.; Stamenkovic, A.; Chan, D.; Chaudhary, R.; Margulets, V.; Edel, A.L.; Hoshijima, M.; et al. Reduction of myocardial ischaemia–reperfusion injury by inactivating oxidized phospholipids. Cardiovasc. Res. 2018, 115, 179–189.
  37. Li, J.-Y.; Liu, S.-Q.; Yao, R.-Q.; Tian, Y.-P.; Yao, Y.-M. A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis. Front. Cell Dev. Biol. 2021, 9, 3421.
  38. Wang, C.; Zhu, L.; Yuan, W.; Sun, L.; Xia, Z.; Zhang, Z.; Yao, W. Diabetes aggravates myocardial ischaemia reperfusion injury via activating Nox2-related programmed cell death in an AMPK-dependent manner. J. Cell. Mol. Med. 2020, 24, 6670–6679.
  39. Lv, Z.; Wang, F.; Zhang, X.; Zhang, X.; Zhang, J.; Liu, R. Etomidate Attenuates the Ferroptosis in Myocardial Ischemia/Reperfusion Rat Model Via Nrf2 Pathway. Shock 2021, 56, 440–449.
  40. Li, W.; Feng, G.; Gauthier, J.M.; Lokshina, I.; Higashikubo, R.; Evans, S.; Liu, X.; Hassan, A.; Tanaka, S.; Cicka, M.; et al. Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation. J. Clin. Investig. 2019, 129, 2293–2304.
  41. Fang, X.; Cai, Z.; Wang, H.; Han, D.; Cheng, Q.; Zhang, P.; Gao, F.; Yu, Y.; Song, Z.; Wu, Q.; et al. Loss of Cardiac Ferritin H Facilitates Cardiomyopathy via Slc7a11-Mediated Ferroptosis. Circ. Res. 2020, 127, 486–501.
  42. Chen, X.; Xu, S.; Zhao, C.; Liu, B. Role of TLR4/NADPH oxidase 4 pathway in promoting cell death through autophagy and ferroptosis during heart failure. Biochem. Biophys. Res. Commun. 2019, 516, 37–43.
  43. Liu, B.; Zhao, C.; Li, H.; Chen, X.; Ding, Y.; Xu, S. Puerarin protects against heart failure induced by pressure overload through mitigation of ferroptosis. Biochem. Biophys. Res. Commun. 2018, 497, 233–240.
  44. Guo, Z.; Ran, Q.; Roberts, L.J.; Zhou, L.; Richardson, A.; Sharan, C.; Wu, D.; Yang, H. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free Radic. Biol. Med. 2008, 44, 343–352.
  45. Bai, T.; Li, M.; Liu, Y.; Qiao, Z.; Wang, Z. Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell. Free Radic. Biol. Med. 2020, 160, 92–102.
  46. Zhou, Y.; Zhou, H.; Hua, L.; Hou, C.; Jia, Q.; Chen, J.; Zhang, S.; Wang, Y.; He, S.; Jia, E. Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis. Free Radic. Biol. Med. 2021, 171, 55–68.
  47. Xie, L.-H.; Gwathmey, J.K.; Zhao, Z. Cardiac adaptation and cardioprotection against arrhythmias and ischemia-reperfusion injury in mammalian hibernators. Pflug. Arch. 2021, 473, 407–416.
  48. Xie, L.-H.; Chen, F.; Karagueuzian, H.S.; Weiss, J.N. Oxidative Stress–Induced Afterdepolarizations and Calmodulin Kinase II Signaling. Circ. Res. 2009, 104, 79–86.
  49. Jacobs, W.; Lammens, M.; Kerckhofs, A.; Voets, E.; Van San, E.; Van Coillie, S.; Peleman, C.; Mergeay, M.; Sirimsi, S.; Matheeussen, V.; et al. Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): Autopsy reveals a ferroptosis signature. ESC Heart Fail. 2020, 7, 3772–3781.
  50. Han, Y.; Zhu, J.; Yang, L.; Nilsson-Payant, B.E.; Hurtado, R.; Lacko, L.A.; Sun, X.; Gade, A.R.; Higgins, C.A.; Sisso, W.J.; et al. SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells. Circ. Res. 2022, 130, 963–977.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Cardiac & Cardiovascular Systems
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Lai-Hua Xie
,
Nadezhda Fefelova
,
Sri Harika Pamarthi
,
Judith K. Gwathmey
View Times: 367
Revisions: 2 times (View History)
Update Date: 07 Sep 2022
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback