{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:01:38Z","timestamp":1780128098995,"version":"3.54.0"},"reference-count":60,"publisher":"IMR Press","issue":"5","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China Key Project","award":["32130109"],"award-info":[{"award-number":["32130109"]}]},{"name":"Funds of Shanghai Sixth People\u2019s Hospital","award":["2017006"],"award-info":[{"award-number":["2017006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Cardiac hypertrophy is a major pathological feature of various cardiovascular diseases. Owing to the simple cardiac structure, rapid development, and genetic tractability, zebrafish are an ideal model for studying cardiac pathology. Zebrafish lacking Bone morphogenetic protein 10 (bmp10-\/-) develop myocardial hypertrophy under normothermic conditions (28 \u00b0C). However, the long-term effects of chronic cold exposure on cardiac function and survival in this model remain unclear. Therefore, this study utilized the bmp10-\/- zebrafish model to systematically evaluate the therapeutic potential of chronic hypothermia in attenuating myocardial hypertrophy and to elucidate the underlying molecular mechanisms. Methods: This study was conducted in three sequential phases. Phase I: bmp10-\/- (homozygous mutant, HO) zebrafish at 6 weeks post-fertilization (wpf) were maintained under normothermic (28 \u00b0C) or hypothermic (15 \u00b0C) conditions for 2 weeks to evaluate the effects of cold exposure on myocardial hypertrophy. Phase II: Building on the Phase I findings, bmp10-\/- zebrafish were subjected to adaptive temperature-switching between normothermic and hypothermic conditions until 10 wpf to assess the temporal effects of cold exposure on cardiac remodeling. Phase III: Pharmacological validation experiments were performed to identify key regulatory genes mediating hypothermia-induced cardioprotection. Results: Long-term cold exposure significantly attenuated myocardial hypertrophy induced by bmp10 deficiency. Given that hypoxia-inducible factor-1 (HIF-1) is a canonical transcriptional regulator of cellular hypoxic responses and that the stability of HIF-1 is tightly controlled by prolyl hydroxylases such as Egl-9 family hypoxia-inducible factor 3 (EGLN3), the involvement of this pathway was further evaluated. These findings indicate that inhibition of EGLN3 activity stabilizes and activates HIF-1 signaling, thereby mediating cardioprotective effects under hypothermic conditions. Conclusions: This study elucidates the functional interplay between the EGLN3 and HIF-1 signaling pathways. Under chronic hypothermia, EGLN3 modulates HIF-1 stability, contributing to the downregulation of BCL2-interacting protein 3 (BNIP3) and facilitating cardiomyocyte injury repair.<\/jats:p>","DOI":"10.31083\/fbl49658","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:25:36Z","timestamp":1780125936000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypothermic Treatment Alleviates Myocardial Hypertrophy in bmp10-\/- Zebrafish"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6703-2430","authenticated-orcid":true,"given":"Fang","family":"Li","sequence":"first","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University, 201306 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7738-6074","authenticated-orcid":true,"given":"Ruiqin","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University, 201306 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6215-2903","authenticated-orcid":true,"given":"Beiqi","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University, 201306 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-687X","authenticated-orcid":true,"given":"Shouwen","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University, 201306 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0717-8536","authenticated-orcid":true,"given":"Liangbiao","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University, 201306 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-5073","authenticated-orcid":true,"given":"Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233 Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Wang L, Rice M, Swist S, Kubin T, Wu F, Wang S, et al. BMP9 and BMP10 Act Directly on Vascular Smooth Muscle Cells for Generation and Maintenance of the Contractile State. Circulation. 2021; 143: 1394\u20131410.","DOI":"10.1161\/CIRCULATIONAHA.120.047375"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Chen H, Brady Ridgway J, Sai T, Lai J, Warming S, Chen H, et al. Context-dependent signaling defines roles of BMP9 and BMP10 in embryonic and postnatal development. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110: 11887\u201311892.","DOI":"10.1073\/pnas.1306074110"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, et al. 2020 AHA\/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2020; 76: e159\u2013e240.","DOI":"10.1016\/j.jacc.2020.08.045"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Zhang W, Chen H, Wang Y, Yong W, Zhu W, Liu Y, et al. Tbx20 transcription factor is a downstream mediator for bone morphogenetic protein-10 in regulating cardiac ventricular wall development and function. The Journal of Biological Chemistry. 2011; 286: 36820\u201336829.","DOI":"10.1074\/jbc.M111.279679"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Chen H, Yong W, Ren S, Shen W, He Y, Cox KA, et al. Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth. The Journal of Biological Chemistry. 2006; 281: 27481\u201327491.","DOI":"10.1074\/jbc.M604818200"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, et al. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell. 2004; 117: 373\u2013386.","DOI":"10.1016\/s0092-8674(04)00405-2"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Mikryukov AA, Mazine A, Wei B, Yang D, Miao Y, Gu M, et al. BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors. Cell Stem Cell. 2021; 28: 96\u2013111.e7.","DOI":"10.1016\/j.stem.2020.10.003"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Chen H, Shi S, Acosta L, Li W, Lu J, Bao S, et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development (Cambridge, England). 2004; 131: 2219\u20132231.","DOI":"10.1242\/dev.01094"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Choi H, Kim BG, Kim YH, Lee SJ, Lee YJ, Oh SP. BMP10 functions independently from BMP9 for the development of a proper arteriovenous network. Angiogenesis. 2023; 26: 167\u2013186.","DOI":"10.1007\/s10456-022-09859-0"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Capasso TL, Li B, Volek HJ, Khalid W, Rochon ER, Anbalagan A, et al. BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance. Angiogenesis. 2020; 23: 203\u2013220.","DOI":"10.1007\/s10456-019-09701-0"},{"key":"ref11","unstructured":"Leggit JC, Whitaker D. Diagnosis and Management of Hypertrophic Cardiomyopathy: Updated Guidelines From the ACC\/AHA. American Family Physician. 2022; 105: 207\u2013209."},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet (London, England). 2013; 381: 242\u2013255.","DOI":"10.1016\/S0140-6736(12)60397-3"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Hu R, Li G, Hu P, Niu H, Li W, Jiang S, et al. bmp10 maintains cardiac function by regulating iron homeostasis. Journal of Genetics and Genomics = Yi Chuan Xue Bao. 2024; 51: 1459\u20131473.","DOI":"10.1016\/j.jgg.2024.10.003"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Grego-Bessa J, Luna-Zurita L, del Monte G, Bol\u00f3s V, Melgar P, Arandilla A, et al. Notch signaling is essential for ventricular chamber development. Developmental Cell. 2007; 12: 415\u2013429.","DOI":"10.1016\/j.devcel.2006.12.011"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Neuhaus H, Rosen V, Thies RS. Heart specific expression of mouse BMP-10 a novel member of the TGF-beta superfamily. Mechanisms of Development. 1999; 80: 181\u2013184.","DOI":"10.1016\/s0925-4773(98)00221-4"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Reyat JS, Chua W, Cardoso VR, Witten A, Kastner PM, Kabir SN, et al. Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation. JCI Insight. 2020; 5: e139179.","DOI":"10.1172\/jci.insight.139179"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Narumanchi S, Wang H, Perttunen S, Tikkanen I, Lakkisto P, Paavola J. Zebrafish Heart Failure Models. Frontiers in Cell and Developmental Biology. 2021; 9: 662583.","DOI":"10.3389\/fcell.2021.662583"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Romano N, Ceci M. Are microRNAs responsible for cardiac hypertrophy in fish and mammals? What we can learn in the activation process in a zebrafish ex vivo model. Biochimica et Biophysica Acta. Molecular Basis of Disease. 2020; 1866: 165896.","DOI":"10.1016\/j.bbadis.2020.165896"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Ceci M, Bonvissuto D, Papetti F, Silvestri F, Sette C, Catalani E, et al. RACK1 contributes to the upregulation of embryonic genes in a model of cardiac hypertrophy. Scientific Reports. 2024; 14: 25698.","DOI":"10.1038\/s41598-024-76138-x"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Jurado-Fasoli L, Sanchez-Delgado G, Di X, Yang W, Kohler I, Villarroya F, et al. Cold-induced changes in plasma signaling lipids are associated with a healthier cardiometabolic profile independently of brown adipose tissue. Cell Reports. Medicine. 2024; 5: 101387.","DOI":"10.1016\/j.xcrm.2023.101387"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Hanssen MJW, Hoeks J, Brans B, van der Lans AAJJ, Schaart G, van den Driessche JJ, et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nature Medicine. 2015; 21: 863\u2013865.","DOI":"10.1038\/nm.3891"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Li X, Wu F, G\u00fcnther S, Looso M, Kuenne C, Zhang T, et al. Inhibition of fatty acid oxidation enables heart regeneration in adult mice. Nature. 2023; 622: 619\u2013626.","DOI":"10.1038\/s41586-023-06585-5"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Shi J, Dai W, Kloner RA. Therapeutic Hypothermia Reduces the Inflammatory Response Following Ischemia\/Reperfusion Injury in Rat Hearts. Therapeutic Hypothermia and Temperature Management. 2017; 7: 162\u2013170.","DOI":"10.1089\/ther.2016.0042"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Hong JM, Lee JS, Song HJ, Jeong HS, Choi HA, Lee K. Therapeutic hypothermia after recanalization in patients with acute ischemic stroke. Stroke. 2014; 45: 134\u2013140.","DOI":"10.1161\/STROKEAHA.113.003143"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Morrell NW, Bloch DB, ten Dijke P, Goumans MJTH, Hata A, Smith J, et al. Targeting BMP signalling in cardiovascular disease and anaemia. Nature Reviews. Cardiology. 2016; 13: 106\u2013120.","DOI":"10.1038\/nrcardio.2015.156"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Dong BB, Li YJ, Liu XY, Huang RT, Yang CX, Xu YJ, et al. Discovery of BMP10 as a new gene underpinning congenital heart defects. American Journal of Translational Research. 2024; 16: 109\u2013125.","DOI":"10.62347\/IVRF4475"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Tanaka K, Honda M, Takabatake T. Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte. Journal of the American College of Cardiology. 2001; 37: 676\u2013685.","DOI":"10.1016\/s0735-1097(00)01123-2"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Hilfiker-Kleiner D, Shukla P, Klein G, Schaefer A, Stapel B, Hoch M, et al. Continuous glycoprotein-130-mediated signal transducer and activator of transcription-3 activation promotes inflammation, left ventricular rupture, and adverse outcome in subacute myocardial infarction. Circulation. 2010; 122: 145\u2013155.","DOI":"10.1161\/CIRCULATIONAHA.109.933127"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Willam C, Maxwell PH, Nichols L, Lygate C, Tian YM, Bernhardt W, et al. HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligation. Journal of Molecular and Cellular Cardiology. 2006; 41: 68\u201377.","DOI":"10.1016\/j.yjmcc.2006.04.009"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Pescador N, Cuevas Y, Naranjo S, Alcaide M, Villar D, Land\u00e1zuri MO, et al. Identification of a functional hypoxia-responsive element that regulates the expression of the egl nine homologue 3 (egln3\/phd3) gene. The Biochemical Journal. 2005; 390: 189\u2013197.","DOI":"10.1042\/BJ20042121"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Jin Y, Pan Y, Zheng S, Liu Y, Xu J, Peng Y, et al. Inactivation of EGLN3 hydroxylase facilitates Erk3 degradation via autophagy and impedes lung cancer growth. Oncogene. 2022; 41: 1752\u20131766.","DOI":"10.1038\/s41388-022-02203-2"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Yang T, Zhang Z, Huang S, Cui M, Liu S, Ding M, et al. Construction of a Zebrafish Model of Cardiac Hypertrophy Caused by ATIC Gene Deletion and Preliminary Exploration of Aerobic Exercise Improvement. International Journal of Molecular Sciences. 2025; 26: 10249.","DOI":"10.3390\/ijms262110249"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Huang L, Gao D, Zhang Y, Wang C, Zuo Z. Exposure to low dose benzo [a] pyrene during early life stages causes symptoms similar to cardiac hypertrophy in adult zebrafish. Journal of hazardous materials. 2014; 276: 377\u2013382.","DOI":"10.1016\/j.jhazmat.2014.05.057"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Fu J, Menzies K, Freeman RS, Taubman MB. EGLN3 prolyl hydroxylase regulates skeletal muscle differentiation and myogenin protein stability. The Journal of Biological Chemistry. 2007; 282: 12410\u201312418.","DOI":"10.1074\/jbc.M608748200"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Sch\u00f6del J, Ratcliffe PJ. Mechanisms of hypoxia signalling: new implications for nephrology. Nature Reviews. Nephrology. 2019; 15: 641\u2013659.","DOI":"10.1038\/s41581-019-0182-z"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Yuan X, Ruan W, Bobrow B, Carmeliet P, Eltzschig HK. Targeting hypoxia-inducible factors: therapeutic opportunities and challenges. Nature Reviews. Drug Discovery. 2024; 23: 175\u2013200.","DOI":"10.1038\/s41573-023-00848-6"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Kong X, Liu H, He X, Sun Y, Ge W. Unraveling the Mystery of Cold Stress-Induced Myocardial Injury. Frontiers in Physiology. 2020; 11: 580811.","DOI":"10.3389\/fphys.2020.580811"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Sluse FE, Jarmuszkiewicz W, Navet R, Douette P, Mathy G, Sluse-Goffart CM. Mitochondrial UCPs: new insights into regulation and impact. Biochimica et Biophysica Acta. 2006; 1757: 480\u2013485.","DOI":"10.1016\/j.bbabio.2006.02.004"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Yenari MA, Hemmen TM. Therapeutic hypothermia for brain ischemia: where have we come and where do we go? Stroke. 2010; 41: S72\u2013S74.","DOI":"10.1161\/STROKEAHA.110.595371"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Zhao MT, Ye S, Su J, Garg V. Cardiomyocyte Proliferation and Maturation: Two Sides of the Same Coin for Heart Regeneration. Frontiers in Cell and Developmental Biology. 2020; 8: 594226.","DOI":"10.3389\/fcell.2020.594226"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Liu Y, Chen X, Zhang HG. Editorial: Cardiac Hypertrophy: From Compensation to Decompensation and Pharmacological Interventions. Frontiers in Pharmacology. 2021; 12: 665936.","DOI":"10.3389\/fphar.2021.665936"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Dansen TB, Burgering BMT. Unravelling the tumor-suppressive functions of FOXO proteins. Trends in Cell Biology. 2008; 18: 421\u2013429.","DOI":"10.1016\/j.tcb.2008.07.004"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"van der Vos KE, Coffer PJ. FOXO-binding partners: it takes two to tango. Oncogene. 2008; 27: 2289\u20132299.","DOI":"10.1038\/onc.2008.22"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Calnan DR, Brunet A. The FoxO code. Oncogene. 2008; 27: 2276\u20132288.","DOI":"10.1038\/onc.2008.21"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Gross DN, van den Heuvel APJ, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008; 27: 2320\u20132336.","DOI":"10.1038\/onc.2008.25"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Strocchi S, Reggiani F, Gobbi G, Ciarrocchi A, Sancisi V. The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation. Oncogene. 2022; 41: 3665\u20133679.","DOI":"10.1038\/s41388-022-02378-8"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Martins R, Lithgow GJ, Link W. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell. 2016; 15: 196\u2013207.","DOI":"10.1111\/acel.12427"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Polytarchou C, Iliopoulos D, Hatziapostolou M, Kottakis F, Maroulakou I, Struhl K, et al. Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Research. 2011; 71: 4720\u20134731.","DOI":"10.1158\/0008-5472.CAN-11-0365"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Li L, Kang H, Zhang Q, D\u2019Agati VD, Al-Awqati Q, Lin F. FoxO3 activation in hypoxic tubules prevents chronic kidney disease. The Journal of Clinical Investigation. 2019; 129: 2374\u20132389.","DOI":"10.1172\/JCI122256"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Nguyen PD, Gooijers I, Campostrini G, Verkerk AO, Honkoop H, Bouwman M, et al. Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration. Science (New York, N.Y.). 2023; 380: 758\u2013764.","DOI":"10.1126\/science.abo6718"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Da\u2019as SI, Hasan W, Salem R, Younes N, Abdelrahman D, Mohamed IA, et al. Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model. International Journal of Molecular Sciences. 2022; 23: 8840.","DOI":"10.3390\/ijms23168840"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death and Differentiation. 2009; 16: 939\u2013946.","DOI":"10.1038\/cdd.2009.16"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA, et al. Response to myocardial ischemia\/reperfusion injury involves Bnip3 and autophagy. Cell Death and Differentiation. 2007; 14: 146\u2013157.","DOI":"10.1038\/sj.cdd.4401936"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, et al. Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death and Differentiation. 2001; 8: 367\u2013376.","DOI":"10.1038\/sj.cdd.4400810"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Gonz\u00e1lez A, Fortu\u00f1o MA, Querejeta R, Ravassa S, L\u00f3pez B, L\u00f3pez N, et al. Cardiomyocyte apoptosis in hypertensive cardiomyopathy. Cardiovascular Research. 2003; 59: 549\u2013562.","DOI":"10.1016\/s0008-6363(03)00498-x"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Rikka S, Quinsay MN, Thomas RL, Kubli DA, Zhang X, Murphy AN, et al. Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death and Differentiation. 2011; 18: 721\u2013731.","DOI":"10.1038\/cdd.2010.146"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Bouillaud F, Alves-Guerra MC, Ricquier D. UCPs, at the interface between bioenergetics and metabolism. Biochimica et Biophysica Acta. 2016; 1863: 2443\u20132456.","DOI":"10.1016\/j.bbamcr.2016.04.013"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Ehata S, Miyazono K. Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years. Frontiers in Cell and Developmental Biology. 2022; 10: 883523.","DOI":"10.3389\/fcell.2022.883523"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Seki T, Yang Y, Sun X, Lim S, Xie S, Guo Z, et al. Brown-fat-mediated tumour suppression by cold-altered global metabolism. Nature. 2022; 608: 421\u2013428.","DOI":"10.1038\/s41586-022-05030-3"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Bouvard C, Tu L, Rossi M, Desroches-Castan A, Berrebeh N, Helfer E, et al. Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10. Cardiovascular Research. 2022; 118: 1805\u20131820.","DOI":"10.1093\/cvr\/cvab187"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/5\/10.31083\/FBL49658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:25:56Z","timestamp":1780125956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/5\/10.31083\/FBL49658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2768-6701(26)02061-7"],"URL":"https:\/\/doi.org\/10.31083\/fbl49658","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"article-number":"49658"}}