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Heavy Metal Scavenger Metallothionein Rescues Against Cold Stress-Evoked Myocardial Contractile Anomalies Through Regulation of Mitophagy

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Abstract

Cold stress prompts an increased prevalence of cardiovascular morbidity yet the underneath machinery remains unclear. Oxidative stress and autophagy appear to contribute to cold stress-induced cardiac anomalies. Our present study evaluated the effect of heavy metal antioxidant metallothionein on cold stress (4 °C)-induced in cardiac remodeling and contractile anomalies and cell signaling involved including regulation of autophagy and mitophagy. Cold stress (3 weeks) prompted interstitial fibrosis, mitochondrial damage (mitochondrial membrane potential and TEM ultrastructure), oxidative stress (glutathione, reactive oxygen species and superoxide), lipid peroxidation, protein injury, elevated left ventricular (LV) end systolic and diastolic diameters, decreased fractional shortening, ejection fraction, Langendorff heart function, cardiomyocyte shortening, maximal velocities of shortening/relengthening, and electrically stimulated intracellular Ca2+ rise along with elongated relaxation duration and intracellular Ca2+ clearance, the responses of which were overtly attenuated or mitigated by metallothionein. Levels of apoptosis, cell death (Bax and loss of Bcl2, IL-18), and autophagy (LC3BII-to-LC3BI ratio, Atg7 and Beclin-1) were overtly upregulated with comparable p62 under cold stress. Cold stress also evoked elevated mitophagy (decreased TOM20, increased Parkin and FUNDC1 with unaltered BNIP3). Cold stress overtly dampened phosphorylation of autophagy/mitophagy inhibitory molecules Akt and mTOR, stimulated and suppressed phosphorylation of ULK1 and eNOS, respectively, in the absence of altered pan protein levels. Cold stress-evoked responses in cell death, autophagy, mitophagy and their regulatory domains were overtly attenuated or ablated by metallothionein. Suppression of autophagy and mitophagy with 3-methyladenine, bafilomycin A1, cyclosporine A, and liensinine rescued hypothermia-instigated cardiomyocyte LC3B puncta formation and mechanical anomalies. Our findings support a protective nature for metallothionein in deep hypothermia-evoked cardiac abnormalities associated with regulation of autophagy and mitophagy.

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Data Availability

The datasets used and/or analyzed supporting the findings of this study are available in this paper or the Supplementary Information. Any other raw data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Fan, J. F., Xiao, Y. C., Feng, Y. F., Niu, L. Y., Tan, X., Sun, J. C., Leng, Y. Q., Li, W. Y., Wang, W. Z., & Wang, Y. K. (2023). A systematic review and meta-analysis of cold exposure and cardiovascular disease outcomes. Front Cardiovasc Med, 10, 1084611.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Abrignani, M. G., Lombardo, A., Braschi, A., Renda, N., & Abrignani, V. (2022). Climatic influences on cardiovascular diseases. World Journal of Cardiology, 14, 152–169.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wu, Q., Yang, M., Wu, K., Su, H., Huang, C., Xu, Z., Ho, H. C., Zheng, H., Zhang, W., Tao, J., Dang, T. A. T., Hossain, M. Z., Khan, M. A., Bogale, D., & Cheng, J. (2023). Abnormal ambient temperature change increases the risk of out-of-hospital cardiac arrest: A systematic review and meta-analysis of exposure types, risk, and vulnerable populations. Science of the Total Environment, 861, 160554.

    Article  CAS  PubMed  ADS  Google Scholar 

  4. Kyokan, M., Bochaton, N., Jirapaet, V., & Pfister, R. E. (2023). Early detection of cold stress to prevent hypothermia: A narrative review. SAGE Open Medicine, 11, 20503121231172864.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cheng, X., & Su, H. (2010). Effects of climatic temperature stress on cardiovascular diseases. European Journal of Internal Medicine, 21, 164–167.

    Article  PubMed  Google Scholar 

  6. Jingesi, M., Lan, S., Hu, J., Dai, M., Huang, S., Chen, S., Liu, N., Lv, Z., Ji, J., Li, X., Wang, P., Cheng, J., Peng, J., & Yin, P. (2023). Association between thermal stress and cardiovascular mortality in the subtropics. International Journal of Biometeorology, 67, 2093–2106.

    Article  PubMed  ADS  Google Scholar 

  7. Kotecki, P., Wieckowska, B., & Stawinska-Witoszynska, B. (2023). The impact of meteorological parameters and seasonal changes on reporting patients with selected cardiovascular diseases to hospital emergency departments: A pilot study. International Journal of Environmental Research and Public Health, 20, 4838.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Barnett, A. G., Dobson, A. J., McElduff, P., Salomaa, V., Kuulasmaa, K., & Sans, S. (2005). Cold periods and coronary events: An analysis of populations worldwide. Journal of Epidemiology and Community Health, 59, 551–557.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kong, X., Liu, H., He, X., Sun, Y., & Ge, W. (2020). Unraveling the mystery of cold stress-induced myocardial injury. Frontiers in Physiology, 11, 580811.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hong, J. H., Kim, K. J., Suzuki, K., & Lee, I. S. (2008). Effect of cold acclimation on antioxidant status in cold acclimated skaters. Journal of Physiological Anthropology, 27, 255–262.

    Article  PubMed  Google Scholar 

  11. Sun, Z. (2010). Cardiovascular responses to cold exposure. Frontiers in Bioscience (Elite Edition), 2, 495–503.

    Article  PubMed  Google Scholar 

  12. Zhang, Y., Li, L., Hua, Y., Nunn, J. M., Dong, F., Yanagisawa, M., & Ren, J. (2012). Cardiac-specific knockout of ETA receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction. Journal of Molecular Cell Biology, 4, 97–107.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yin, Z., Ding, G., Chen, X., Qin, X., Xu, H., Zeng, B., Ren, J., Zheng, Q., & Wang, S. (2020). Beclin1 haploinsufficiency rescues low ambient temperature-induced cardiac remodeling and contractile dysfunction through inhibition of ferroptosis and mitochondrial injury. Metabolism, 113, 154397.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang, Y., Hu, N., Hua, Y., Richmond, K. L., Dong, F., & Ren, J. (2012). Cardiac overexpression of metallothionein rescues cold exposure-induced myocardial contractile dysfunction through attenuation of cardiac fibrosis despite cardiomyocyte mechanical anomalies. Free Radical Biology & Medicine, 53, 194–207.

    Article  CAS  Google Scholar 

  15. Cai, L., Wang, Y., Zhou, G., Chen, T., Song, Y., Li, X., & Kang, Y. J. (2006). Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. Journal of the American College of Cardiology, 48, 1688–1697.

    Article  CAS  PubMed  Google Scholar 

  16. Dong, F., Li, Q., Sreejayan, N., Nunn, J. M., & Ren, J. (2007). Metallothionein prevents high-fat diet induced cardiac contractile dysfunction: Role of peroxisome proliferator activated receptor gamma coactivator 1alpha and mitochondrial biogenesis. Diabetes, 56, 2201–2212.

    Article  CAS  PubMed  Google Scholar 

  17. Fang, C. X., Dong, F., Ren, B. H., Epstein, P. N., & Ren, J. (2005). Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: Role of Akt phosphorylation, PTB1B, PPARgamma and c-Jun. Diabetologia, 48, 2412–2421.

    Article  CAS  PubMed  Google Scholar 

  18. Fang, C. X., Doser, T. A., Yang, X., Sreejayan, N., & Ren, J. (2006). Metallothionein antagonizes aging-induced cardiac contractile dysfunction: Role of PTP1B, insulin receptor tyrosine phosphorylation and Akt. Aging Cell, 5, 177–185.

    Article  CAS  PubMed  Google Scholar 

  19. Wang, J., Song, Y., Elsherif, L., Song, Z., Zhou, G., Prabhu, S. D., Saari, J. T., & Cai, L. (2006). Cardiac metallothionein induction plays the major role in the prevention of diabetic cardiomyopathy by zinc supplementation. Circulation, 113, 544–554.

    Article  CAS  PubMed  Google Scholar 

  20. Wang, Y., Feng, W., Xue, W., Tan, Y., Hein, D. W., Li, X. K., & Cai, L. (2009). Inactivation of GSK-3beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes, 58, 1391–1402.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yang, X., Doser, T. A., Fang, C. X., Nunn, J. M., Janardhanan, R., Zhu, M., Sreejayan, N., Quinn, M. T., & Ren, J. (2006). Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: Role of oxidative stress. The FASEB Journal, 20, 1024–1026.

    Article  CAS  PubMed  Google Scholar 

  22. Chen, Y., Zhao, J., Ye, H., Ceylan-Isik, A. F., Zhang, B., Liu, Q., Yang, Y., Dong, M., Luo, B., & Ren, J. (2023). Beneficial impact of cardiac heavy metal scavenger metallothionein in sepsis-provoked cardiac anomalies dependent upon regulation of endoplasmic reticulum stress and ferroptosis but not autophagy. Life Sciences, 336, 122291.

    Article  PubMed  Google Scholar 

  23. Ajoolabady, A., Chiong, M., Lavandero, S., Klionsky, D. J., & Ren, J. (2022). Mitophagy in cardiovascular diseases: Molecular mechanisms, pathogenesis, and treatment. Trends in Molecular Medicine, 28, 836–849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ren, J., & Zhang, Y. (2018). Targeting autophagy in aging and aging-related cardiovascular diseases. Trends in Pharmacological Sciences, 39, 1064–1076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ruperez, C., Blasco-Roset, A., Kular, D., Cairo, M., Ferrer-Curriu, G., Villarroya, J., Zamora, M., Crispi, F., Villarroya, F., & Planavila, A. (2022). Autophagy is involved in cardiac remodeling in response to environmental temperature change. Frontiers in Physiology, 13, 864427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ge, W., Guo, R., & Ren, J. (2011). AMP-dependent kinase and autophagic flux are involved in aldehyde dehydrogenase-2-induced protection against cardiac toxicity of ethanol. Free Radical Biology & Medicine, 51, 1736–1748.

    Article  CAS  Google Scholar 

  27. Wei, X., Qi, Y., Zhang, X., Gu, X., Cai, H., Yang, J., & Zhang, Y. (2015). ROS act as an upstream signal to mediate cadmium-induced mitophagy in mouse brain. Neurotoxicology, 46, 19–24.

    Article  CAS  PubMed  Google Scholar 

  28. Liang, X., Wang, S., Wang, L., Ceylan, A. F., Ren, J., & Zhang, Y. (2020). Mitophagy inhibitor liensinine suppresses doxorubicin-induced cardiotoxicity through inhibition of Drp1-mediated maladaptive mitochondrial fission. Pharmacological Research, 157, 104846.

    Article  CAS  PubMed  Google Scholar 

  29. Ye, G., Metreveli, N. S., Ren, J., & Epstein, P. N. (2003). Metallothionein prevents diabetes-induced deficits in cardiomyocytes by inhibiting reactive oxygen species production. Diabetes, 52, 777–783.

    Article  CAS  PubMed  Google Scholar 

  30. Wold, L. E., Ceylan-Isik, A. F., Fang, C. X., Yang, X., Li, S. Y., Sreejayan, N., Privratsky, J. R., & Ren, J. (2006). Metallothionein alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of Ca2+ cycling proteins, NADPH oxidase, poly(ADP-Ribose) polymerase and myosin heavy chain isozyme. Free Radical Biology & Medicine, 40, 1419–1429.

    Article  CAS  Google Scholar 

  31. Chen, G. F., & Sun, Z. (2006). Effects of chronic cold exposure on the endothelin system. Journal of Applied Physiology, 100, 1719–1726.

    Article  CAS  PubMed  Google Scholar 

  32. Doyle, A., Zhang, G., Abdel Fattah, E. A., Eissa, N. T., & Li, Y. P. (2011). Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways. The FASEB Journal, 25, 99–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jiang, S., Guo, R., Zhang, Y., Zou, Y., & Ren, J. (2013). Heavy metal scavenger metallothionein mitigates deep hypothermia-induced myocardial contractile anomalies: Role of autophagy. American journal of physiology. Endocrinology and metabolism, 304, E74-86.

    Article  CAS  PubMed  Google Scholar 

  34. Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43, e47.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ringner, M. (2008). What is principal component analysis? Nature Biotechnology, 26, 303–304.

    Article  CAS  PubMed  Google Scholar 

  36. Guo, R., Ma, H., Gao, F., Zhong, L., & Ren, J. (2009). Metallothionein alleviates oxidative stress-induced endoplasmic reticulum stress and myocardial dysfunction. Journal of Molecular and Cellular Cardiology, 47, 228–237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ren, J., & Wold, L. E. (2001). Measurement of cardiac mechanical function in isolated ventricular myocytes from rats and mice by computerized video-based imaging. Biol Proced Online, 3, 43–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang, Q., Yang, L., Hua, Y., Nair, S., Xu, X., & Ren, J. (2014). AMP-activated protein kinase deficiency rescues paraquat-induced cardiac contractile dysfunction through an autophagy-dependent mechanism. Toxicological Sciences, 142, 6–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Guo, R., Hu, N., Kandadi, M. R., & Ren, J. (2012). Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts. Autophagy, 8, 593–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu, Y., You, F., Song, G., Ceylan, A. F., Deng, Q., Jin, W., Min, J., Burd, L., Ren, J., & Pei, Z. (2022). Deficiency in Beclin1 attenuates alcohol-induced cardiac dysfunction via inhibition of ferroptosis. Biochimica et Biophysica Acta - General Subjects, 1866, 130245.

    Article  CAS  PubMed  Google Scholar 

  41. Xu, H., Yu, W., Sun, S., Li, C., Ren, J., & Zhang, Y. (2021). TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner. Science Bull, 66, 1669–1683.

    Article  CAS  ADS  Google Scholar 

  42. Zhang, Y., Babcock, S. A., Hu, N., Maris, J. R., Wang, H., & Ren, J. (2012). Mitochondrial aldehyde dehydrogenase (ALDH2) protects against streptozotocin-induced diabetic cardiomyopathy: Role of GSK3beta and mitochondrial function. BMC Medicine, 10, 40.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ren, J., Privratsky, J. R., Yang, X., Dong, F., & Carlson, E. C. (2008). Metallothionein alleviates glutathione depletion-induced oxidative cardiomyopathy in murine hearts. Critical Care Medicine, 36, 2106–2116.

    Article  CAS  PubMed  Google Scholar 

  44. Ren, J. (2007). Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats. Clinical and Experimental Pharmacology and Physiology, 34, 432–438.

    Article  CAS  PubMed  Google Scholar 

  45. Qin, Z., Wang, P., Chen, W., Wang, J. R., Ma, X., Zhang, H., Zhang, W. J., & Wei, C. (2023). Hepatic ELOVL3 is dispensable for lipid metabolism in mice. Biochemical and Biophysical Research Communications, 658, 128–135.

    Article  CAS  PubMed  Google Scholar 

  46. Pivtoraiko, V. N., Harrington, A. J., Mader, B. J., Luker, A. M., Caldwell, G. A., Caldwell, K. A., Roth, K. A., & Shacka, J. J. Low-dose bafilomycin attenuates neuronal cell death associated with autophagy-lysosome pathway dysfunction. J Neurochem, 114, 1193–1204.

  47. Templeman, N. M., Beaudry, J. L., Le Moine, C. M., & McClelland, G. B. (2010). Chronic hypoxia- and cold-induced changes in cardiac enzyme and gene expression in CD-1 mice. Biochimica et Biophysica Acta, 1800, 1248–1255.

    Article  CAS  PubMed  Google Scholar 

  48. Williams, B., Kabbage, M., Britt, R., & Dickman, M. B. (2010). AtBAG7, an Arabidopsis Bcl-2-associated athanogene, resides in the endoplasmic reticulum and is involved in the unfolded protein response. Proc Natl Acad Sci U S A, 107, 6088–6093.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  49. Kim, J., Kundu, M., Viollet, B., & Guan, K. L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biology, 13, 132–141.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  50. Sarkar, S., Korolchuk, V. I., Renna, M., Imarisio, S., Fleming, A., Williams, A., Garcia-Arencibia, M., Rose, C., Luo, S., Underwood, B. R., Kroemer, G., O’Kane, C. J., & Rubinsztein, D. C. (2011). Complex inhibitory effects of nitric oxide on autophagy. Molecular Cell, 43, 19–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Li, Q., & Ren, J. (2006). Cardiac overexpression of metallothionein attenuates chronic alcohol intake-induced cardiomyocyte contractile dysfunction. Cardiovascular Toxicology, 6, 173–182.

    Article  CAS  PubMed  Google Scholar 

  52. Oudit, G. Y., & Penninger, J. M. (2009). Cardiac regulation by phosphoinositide 3-kinases and PTEN. Cardiovascular Research, 82, 250–260.

    Article  CAS  PubMed  Google Scholar 

  53. Nemchenko, A., Chiong, M., Turer, A., Lavandero, S., & Hill, J. A. (2011). Autophagy as a therapeutic target in cardiovascular disease. Journal of Molecular and Cellular Cardiology, 51, 584–593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Xu, X., & Ren, J. (2012). Unmasking the janus faces of autophagy in obesity-associated insulin resistance and cardiac dysfunction. Clinical and Experimental Pharmacology and Physiology, 39, 200–208.

    Article  CAS  PubMed  Google Scholar 

  55. Huang, J., Lam, G. Y., & Brumell, J. H. (2011). Autophagy signaling through reactive oxygen species. Antioxidants & Redox Signaling, 14, 2215–2231.

    Article  CAS  Google Scholar 

  56. Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023). Mitophagy in human health, ageing and disease. Nature Metabolism.

  57. Monsieurs, K.G., Nolan, J.P., Bossaert, L.L., Greif, R., Maconochie, I.K., Nikolaou, N.I., Perkins, G.D., Soar, J., Truhlar, A., Wyllie, J., Zideman, D.A. and Group, E.R.C.G.W. (2015). European resuscitation council guidelines for resuscitation 2015: Section 1. Executive summary. Resuscitation, 95, 1–80.

    Google Scholar 

  58. Keller, K., Sagoschen, I., Schmitt, V. H., Munzel, T., Gori, T., & Hobohm, L. (2022). Hypothermia and its role in patients with ST-segment-elevation myocardial infarction and cardiac arrest. Front Cardiovasc Med, 9, 1051978.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Ibanez, B., James, S., Agewall, S., Antunes, M.J., Bucciarelli-Ducci, C., Bueno, H., Caforio, A.L.P., Crea, F., Goudevenos, J.A., Halvorsen, S., Hindricks, G., Kastrati, A., Lenzen, M.J., Prescott, E., Roffi, M., Valgimigli, M., Varenhorst, C., Vranckx, P., Widimsky, P. and Group, E.S.C.S.D. (2018). 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal, 39, 119–177.

    Article  Google Scholar 

  60. McCormick, J. J., Meade, R. D., King, K. E., Notley, S. R., Akerman, A. P., Sigal, R. J., & Kenny, G. P. (2023). Brief ambient cooling preserves autophagy in peripheral blood mononuclear cells from older adults during 9 h of heat exposure. Journal of Applied Physiology, 1985(135), 969–976.

    Article  Google Scholar 

  61. Sun, G., Su, W., Bao, J., Teng, T., Song, X., Wang, J., & Shi, B. (2023). Dietary full-fat rice bran prevents the risk of heart ferroptosis and imbalance of energy metabolism induced by prolonged cold stimulation. Food & Function, 14, 1530–1544.

    Article  CAS  Google Scholar 

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Acknowledgements

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Funding

This work was supported in part by grants from the Natural Science Foundation of China (82060351) and Natural Science Foundation of Jiangxi Province (20203BBGL73189).

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  1. Zhaohui Pei, Yayuan Xiong, and Shasha Jiang have contributed equally to this work.

Authors and Affiliations

  1. The Second Department of Cardiology, Nanchang City Renmin Hospital, Nanchang, 3330009, China

    Zhaohui Pei, Wei Jin & Yan Gong

  2. The First Department of Cardiology, Nanchang City Renmin Hospital, Nanchang, 3330009, China

    Yayuan Xiong

  3. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Shasha Jiang & Yunzeng Zou

  4. College of Life Sciences, Institute of Life Science and Green Development, Hebei University, Baoding, China

    Rui Guo

  5. The Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding, China

    Rui Guo

  6. Department of Cardiovascular Surgery, Sun Yat–Sen Memorial Hospital, Sun Yat–Sen University, Guangzhou, 510000, China

    Jun Tao

  7. Shanghai Institute for Cardiovascular Diseases, Shanghai, 200032, China

    Zhenzhong Zhang, Yingmei Zhang, Yunzeng Zou & Jun Ren

  8. National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China

    Zhenzhong Zhang, Yingmei Zhang, Yunzeng Zou & Jun Ren

  9. Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai, 200032, China

    Yingmei Zhang, Yunzeng Zou & Jun Ren

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  1. Zhaohui Pei
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ZP, YX, SJ, RG, WJ, JT, ZZ and YZ data collection and analysis; YZ and YG: helpful discussion; ZP and JR manuscript drafting, editing and supervision of the study.

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Pei, Z., Xiong, Y., Jiang, S. et al. Heavy Metal Scavenger Metallothionein Rescues Against Cold Stress-Evoked Myocardial Contractile Anomalies Through Regulation of Mitophagy. Cardiovasc Toxicol 24, 85–101 (2024). https://doi.org/10.1007/s12012-023-09823-4

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