{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:20:24Z","timestamp":1787239224333,"version":"build-2736575974"},"reference-count":61,"publisher":"Pharmaceutical Society of Japan","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2026,1,1]]},"DOI":"10.1248\/bpb.b25-00481","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T22:08:57Z","timestamp":1767218937000},"page":"24-29","source":"Crossref","is-referenced-by-count":3,"title":["Cardioprotective Role of Neuregulin1\u2013ErbB2 Signaling Pathway: Its Physiological and Onco-Cardiological Roles in the Heart"],"prefix":"10.1248","volume":"49","author":[{"given":"Yoshinori","family":"Mikami","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Toho University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Adachi-Akahane","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Toho University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. <i>Nature<\/i>, <b>378<\/b>, 386\u2013390 (1995).","DOI":"10.1038\/378386a0"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Odiete O, Hill MF, Sawyer DB. Neuregulin in cardiovascular development and disease. <i>Circ. Res.<\/i>, <b>111<\/b>, 1376\u20131385 (2012).","DOI":"10.1161\/CIRCRESAHA.112.267286"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Geissler A, Ryzhov S, Sawyer DB. Neuregulins: protective and reparative growth factors in multiple forms of cardiovascular disease. <i>Clin. Sci.<\/i>, <b>134<\/b>, 2623\u20132643 (2020).","DOI":"10.1042\/CS20200230"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2\/<i>neu<\/i> oncogene. <i>Science<\/i>, <b>235<\/b>, 177\u2013182 (1987).","DOI":"10.1126\/science.3798106"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF. Studies of the HER-2\/<i>neu<\/i> proto-oncogene in human breast and ovarian cancer. <i>Science<\/i>, <b>244<\/b>, 707\u2013712 (1989).","DOI":"10.1126\/science.2470152"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Krishnamurti U, Silverman JF. HER2 in breast cancer: a review and update. <i>Adv. Anat. Pathol.<\/i>, <b>21<\/b>, 100\u2013107 (2014).","DOI":"10.1097\/PAP.0000000000000015"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. <i>Nature<\/i>, <b>421<\/b>, 756\u2013760 (2003).","DOI":"10.1038\/nature01392"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. <i>Ann. Oncol.<\/i>, <b>19<\/b>, 1523\u20131529 (2008).","DOI":"10.1093\/annonc\/mdn169"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. <i>J. Clin. Oncol.<\/i>, <b>23<\/b>, 7811\u20137819 (2005).","DOI":"10.1200\/JCO.2005.02.4091"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D. Cardiac dysfunction in the trastuzumab clinical trials experience. <i>J. Clin. Oncol.<\/i>, <b>20<\/b>, 1215\u20131221 (2002).","DOI":"10.1200\/JCO.2002.20.5.1215"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Hahn VS, Zhang KW, Sun L, Narayan V, Lenihan DJ, Ky B. Heart failure with targeted cancer therapies: mechanisms and cardioprotection. <i>Circ. Res.<\/i>, <b>128<\/b>, 1576\u20131593 (2021).","DOI":"10.1161\/CIRCRESAHA.121.318223"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Udagawa C, Kuah S, Shimoi T, Kato K, Yoshida T, Nakano MH, Shimo A, Kojima Y, Yoshie R, Tsugawa K, Mushiroda T, Tan EY, Zembutsu H. Replication study for the association of five SNPs identified by GWAS and trastuzumab-induced cardiotoxicity in Japanese and singaporean cohorts. <i>Biol. Pharm. Bull.<\/i>, <b>45<\/b>, 1198\u20131202 (2022).","DOI":"10.1248\/bpb.b22-00136"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Falls DL. Neuregulins: functions, forms, and signaling strategies. <i>Exp. Cell Res.<\/i>, <b>284<\/b>, 14\u201330 (2003).","DOI":"10.1016\/S0014-4827(02)00102-7"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Lemmens K, Doggen K, De Keulenaer GW. Role of neuregulin-1\/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure. <i>Circulation<\/i>, <b>116<\/b>, 954\u2013960 (2007).","DOI":"10.1161\/CIRCULATIONAHA.107.690487"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Gum\u00e0 A, Mart\u00ednez-Redondo V, L\u00f3pez-Soldado I, Cant\u00f3 C, Zorzano A. Emerging role of neuregulin as a modulator of muscle metabolism. <i>Am. J. Physiol. Endocrinol. Metab.<\/i>, <b>298<\/b>, E742\u2013E750 (2010).","DOI":"10.1152\/ajpendo.00541.2009"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Horiuchi K, Zhou HM, Kelly K, Manova K, Blobel CP. Evaluation of the contributions of ADAMs 9, 12, 15, 17, and 19 to heart development and ectodomain shedding of neuregulins \u03b21 and \u03b22. <i>Dev. Biol.<\/i>, <b>283<\/b>, 459\u2013471 (2005).","DOI":"10.1016\/j.ydbio.2005.05.004"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Jones JT, Ballinger MD, Pisacane PI, Lofgren JA, Fitzpatrick VD, Fairbrother WJ, Wells JA, Sliwkowski MX. Binding interaction of the heregulin\u03b2 <i>egf<\/i> domain with ErbB3 and ErbB4 receptors assessed by alanine scanning mutagenesis. <i>J. Biol. Chem.<\/i>, <b>273<\/b>, 11667\u201311674 (1998).","DOI":"10.1074\/jbc.273.19.11667"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Lemmens K, Segers VF, Demolder M, De Keulenaer GW. Role of neuregulin-1\/ErbB2 signaling in endothelium-cardiomyocyte cross-talk. <i>J. Biol. Chem.<\/i>, <b>281<\/b>, 19469\u201319477 (2006).","DOI":"10.1074\/jbc.M600399200"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Mikami Y, Iwase F, Ohshima D, Tomida T, Adachi-Akahane S. Compensatory role of neuregulin-1 in diabetic cardiomyopathy. <i>J. Pharmacol. Sci.<\/i>, <b>153<\/b>, 130\u2013141 (2023).","DOI":"10.1016\/j.jphs.2023.08.009"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Liu P, Cleveland TE 4th, Bouyain S, Byrne PO, Longo PA, Leahy DJ. A single ligand is sufficient to activate EGFR dimers. <i>Proc. Natl. Acad. Sci. U.S.A.<\/i>, <b>109<\/b>, 10861\u201310866 (2012).","DOI":"10.1073\/pnas.1201114109"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Diwanji D, Trenker R, Thaker TM, Wang F, Agard DA, Verba KA, Jura N. Structures of the HER2-HER3-NRG1\u03b2 complex reveal a dynamic dimer interface. <i>Nature<\/i>, <b>600<\/b>, 339\u2013343 (2021).","DOI":"10.1038\/s41586-021-04084-z"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Kumagai S, Koyama S, Nishikawa H. Antitumour immunity regulated by aberrant ERBB family signalling. <i>Nat. Rev. Cancer<\/i>, <b>21<\/b>, 181\u2013197 (2021).","DOI":"10.1038\/s41568-020-00322-0"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Mei L, Xiong WC. Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. <i>Nat. Rev. Neurosci.<\/i>, <b>9<\/b>, 437\u2013452 (2008).","DOI":"10.1038\/nrn2392"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Ma H, Yin C, Zhang Y, Qian L, Liu J. ErbB2 is required for cardiomyocyte proliferation in murine neonatal hearts. <i>Gene<\/i>, <b>592<\/b>, 325\u2013330 (2016).","DOI":"10.1016\/j.gene.2016.07.006"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Lee KF, Simon H, Chen H, Bates B, Hung MC, Hauser C. Requirement for neuregulin receptor erbB2 in neural and cardiac development. <i>Nature<\/i>, <b>378<\/b>, 394\u2013398 (1995).","DOI":"10.1038\/378394a0"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klein R, Lemke G. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. <i>Nature<\/i>, <b>378<\/b>, 390\u2013394 (1995).","DOI":"10.1038\/378390a0"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Nakaoka Y, Nishida K, Narimatsu M, Kamiya A, Minami T, Sawa H, Okawa K, Fujio Y, Koyama T, Maeda M, Sone M, Yamasaki S, Arai Y, Koh GY, Kodama T, Hirota H, Otsu K, Hirano T, Mochizuki N. Gab family proteins are essential for postnatal maintenance of cardiac function <i>via<\/i> neuregulin-1\/ErbB signaling. <i>J. Clin. Invest.<\/i>, <b>117<\/b>, 1771\u20131781 (2007).","DOI":"10.1172\/JCI30651"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Crone SA, Zhao YY, Fan L, Gu Y, Minamisawa S, Liu Y, Peterson KL, Chen J, Kahn R, Condorelli G, Ross J Jr, Chien KR, Lee KF. ErbB2 is essential in the prevention of dilated cardiomyopathy. <i>Nat. Med.<\/i>, <b>8<\/b>, 459\u2013465 (2002).","DOI":"10.1038\/nm0502-459"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Hedhli N, Huang Q, Kalinowski A, Palmeri M, Hu X, Russell RR, Russell KS. Endothelium-derived neuregulin protects the heart against ischemic injury. <i>Circulation<\/i>, <b>123<\/b>, 2254\u20132262 (2011).","DOI":"10.1161\/CIRCULATIONAHA.110.991125"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Liu FF, Stone JR, Schuldt AJ, Okoshi K, Okoshi MP, Nakayama M, Ho KK, Manning WJ, Marchionni MA, Lorell BH, Morgan JP, Yan X. Heterozygous knockout of neuregulin-1 gene in mice exacerbates doxorubicin-induced heart failure. <i>Am. J. Physiol. Heart Circ. Physiol.<\/i>, <b>289<\/b>, H660\u2013H666 (2005).","DOI":"10.1152\/ajpheart.00268.2005"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Ad\u00e3o R, Mendes-Ferreira P, Maia-Rocha C, Santos-Ribeiro D, Rodrigues PG, Vidal-Meireles A, Monteiro-Pinto C, Pimentel LD, Falcao-Pires I, De Keulenaer GW, Leite-Moreira AF, Bras-Silva C. Neuregulin-1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension. <i>Clin. Exp. Pharmacol. Physiol.<\/i>, <b>46<\/b>, 255\u2013265 (2019).","DOI":"10.1111\/1440-1681.13043"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) De Keulenaer GW, Feyen E, Dugaucquier L, Shakeri H, Shchendrygina A, Belenkov YN, Brink M, Vermeulen Z, Segers VFM. Mechanisms of the multitasking endothelial protein NRG-1 as a compensatory factor during chronic heart failure. <i>Circ. Heart Fail.<\/i>, <b>12<\/b>, e006288 (2019).","DOI":"10.1161\/CIRCHEARTFAILURE.119.006288"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Bersell K, Arab S, Haring B, Kuhn B. Neuregulin1\/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. <i>Cell<\/i>, <b>138<\/b>, 257\u2013270 (2009).","DOI":"10.1016\/j.cell.2009.04.060"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Liu X, Gu X, Li Z, Li X, Li H, Chang J, Chen P, Jin J, Xi B, Chen D, Lai D, Graham RM, Zhou M. Neuregulin-1\/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. <i>J. Am. Coll. Cardiol.<\/i>, <b>48<\/b>, 1438\u20131447 (2006).","DOI":"10.1016\/j.jacc.2006.05.057"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Gu X, Liu X, Xu D, Li X, Yan M, Qi Y, Yan W, Wang W, Pan J, Xu Y, Xi B, Cheng L, Jia J, Wang K, Ge J, Zhou M. Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin. <i>Cardiovasc. Res.<\/i>, <b>88<\/b>, 334\u2013343 (2010).","DOI":"10.1093\/cvr\/cvq223"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Jabbour A, Hayward CS, Keogh AM, Kotlyar E, McCrohon JA, England JF, Amor R, Liu X, Li XY, Zhou MD, Graham RM, Macdonald PS. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. <i>Eur. J. Heart Fail.<\/i>, <b>13<\/b>, 83\u201392 (2011).","DOI":"10.1093\/eurjhf\/hfq152"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Gao R, Zhang J, Cheng L, Wu X, Dong W, Yang X, Li T, Liu X, Xu Y, Li X, Zhou M. A Phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. <i>J. Am. Coll. Cardiol.<\/i>, <b>55<\/b>, 1907\u20131914 (2010).","DOI":"10.1016\/j.jacc.2009.12.044"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF 3rd, Hynes NE. The ErbB2\/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. <i>Proc. Natl. Acad. Sci. U.S.A.<\/i>, <b>100<\/b>, 8933\u20138938 (2003).","DOI":"10.1073\/pnas.1537685100"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Baselga J, Swain SM. Novel anti-cancer targets: revisiting ERBB2 and discovering ERBB3. <i>Nat. Rev. Cancer<\/i>, <b>9<\/b>, 463\u2013475 (2009).","DOI":"10.1038\/nrc2656"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Jay SM, Kurtagic E, Alvarez LM, de Picciotto S, Sanchez E, Hawkins JF, Prince RN, Guerrero Y, Treasure CL, Lee RT, Griffith LG. Engineered bivalent ligands to bias ErbB receptor-mediated signaling and phenotypes. <i>J. Biol. Chem.<\/i>, <b>286<\/b>, 27729\u201327740 (2011).","DOI":"10.1074\/jbc.M111.221093"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Jay SM, Murthy AC, Hawkins JF, Wortzel JR, Steinhauser ML, Alvarez LM, Gannon J, Macrae CA, Griffith LG, Lee RT. An engineered bivalent neuregulin protects against doxorubicin-induced cardiotoxicity with reduced proneoplastic potential. <i>Circulation<\/i>, <b>128<\/b>, 152\u2013161 (2013).","DOI":"10.1161\/CIRCULATIONAHA.113.002203"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Cools JMT, Goovaerts BK, Feyen E, Van den Bogaert S, Fu Y, Civati C, Van Fraeyenhove J, Tubeeckx MRL, Ott J, Nguyen L, W\u00fclfers EM, Van Berlo B, De Vries AAF, Vandersickel N, Pijnappels DA, Audenaert D, Roderick HL, De Winter H, De Keulenaer GW, Segers VFM. Small-molecule-induced ERBB4 activation to treat heart failure. <i>Nat. Commun.<\/i>, <b>16<\/b>, 576 (2025).","DOI":"10.1038\/s41467-024-54908-5"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Ewer MS, Lippman SM. Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity. <i>J. Clin. Oncol.<\/i>, <b>23<\/b>, 2900\u20132902 (2005).","DOI":"10.1200\/JCO.2005.05.827"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Dempsey N, Rosenthal A, Dabas N, Kropotova Y, Lippman M, Bishopric NH. Trastuzumab-induced cardiotoxicity: a review of clinical risk factors, pharmacologic prevention, and cardiotoxicity of other HER2-directed therapies. <i>Breast Cancer Res. Treat.<\/i>, <b>188<\/b>, 21\u201336 (2021).","DOI":"10.1007\/s10549-021-06280-x"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45) Moudgil R, Haddad H. Chemotherapy-related cardiac dysfunction: grey area in type I and type II classification. <i>Curr. Opin. Cardiol.<\/i>, <b>32<\/b>, 181\u2013188 (2017).","DOI":"10.1097\/HCO.0000000000000361"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46) Lechuga-Noa VE, Rodriguez-Tanta LY, Solis-Yucra TDP, Rojo Rosales EC. Irreversible cardiotoxicity induced by trastuzumab: a systematic review based on a pharmacovigilance case report. <i>Arch. Peru. Cardiol. Cir. Cardiovasc.<\/i>, <b>6<\/b>, 1\u201310 (2025).","DOI":"10.47487\/apcyccv.v6i1.456"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47) Ezaz G, Long JB, Gross CP, Chen J. Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. <i>J. Am. Heart Assoc.<\/i>, <b>3<\/b>, e000472 (2014).","DOI":"10.1161\/JAHA.113.000472"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48) Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. <i>N. Engl. J. Med.<\/i>, <b>344<\/b>, 783\u2013792 (2001).","DOI":"10.1056\/NEJM200103153441101"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49) Koulaouzidis G, Yung AE, Yung DE, Skonieczna-Zydecka K, Marlicz W, Koulaouzidis A, Charisopoulou D. Conventional cardiac risk factors associated with trastuzumab-induced cardiotoxicity in breast cancer: Systematic review and meta-analysis. <i>Curr. Probl. Cancer<\/i>, <b>45<\/b>, 100723 (2021).","DOI":"10.1016\/j.currproblcancer.2021.100723"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50) Jawa Z, Perez RM, Garlie L, Singh M, Qamar R, Khandheria BK, Jahangir A, Shi Y. Risk factors of trastuzumab-induced cardiotoxicity in breast cancer: a meta-analysis. <i>Medicine<\/i>, <b>95<\/b>, e5195 (2016).","DOI":"10.1097\/MD.0000000000005195"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51) Serrano C, Cort\u00e9s J, De Mattos-Arruda L, Bellet M, G\u00f3mez P, Saura C, P\u00e9rez J, Vidal M, Mu\u00f1oz-Couselo E, Carreras MJ, S\u00e1nchez-Oll\u00e9 G, Tabernero J, Baselga J, Di Cosimo S. Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. <i>Ann. Oncol.<\/i>, <b>23<\/b>, 897\u2013902 (2012).","DOI":"10.1093\/annonc\/mdr348"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52) Hamaguchi S, Abe K, Komatsu M, Kainuma J, Namekata I, Tanaka H. Positive lusitropic effect of quercetin on isolated ventricular myocardia from normal and streptozotocin-induced diabetic mice. <i>Biol. Pharm. Bull.<\/i>, <b>44<\/b>, 1894\u20131897 (2021).","DOI":"10.1248\/bpb.b21-00580"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53) Greco S, Fasanaro P, Castelvecchio S, D\u2019Alessandra Y, Arcelli D, Di Donato M, Malavazos A, Capogrossi MC, Menicanti L, Martelli F. MicroRNA dysregulation in diabetic ischemic heart failure patients. <i>Diabetes<\/i>, <b>61<\/b>, 1633\u20131641 (2012).","DOI":"10.2337\/db11-0952"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54) Doggen K, Ray L, Mathieu M, Mc Entee K, Lemmens K, De Keulenaer GW. Ventricular ErbB2\/ErbB4 activation and downstream signaling in pacing-induced heart failure. <i>J. Mol. Cell. Cardiol.<\/i>, <b>46<\/b>, 33\u201338 (2009).","DOI":"10.1016\/j.yjmcc.2008.10.010"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55) Ky B, Kimmel SE, Safa RN, Putt ME, Sweitzer NK, Fang JC, Sawyer DB, Cappola TP. Neuregulin-1\u03b2 is associated with disease severity and adverse outcomes in chronic heart failure. <i>Circulation<\/i>, <b>120<\/b>, 310\u2013317 (2009).","DOI":"10.1161\/CIRCULATIONAHA.109.856310"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56) Rohrbach S, Niemann B, Silber RE, Holtz J. Neuregulin receptors erbB2 and erbB4 in failing human myocardium\u2014depressed expression and attenuated activation. <i>Basic Res. Cardiol.<\/i>, <b>100<\/b>, 240\u2013249 (2005).","DOI":"10.1007\/s00395-005-0514-4"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57) Miao J, Huang S, Su YR, Lenneman CA, Wright M, Harrell FE, Sawyer DB, Lenihan DJ. Effects of endogenous serum neuregulin-1\u03b2 on morbidity and mortality in patients with heart failure and left ventricular systolic dysfunction. <i>Biomarkers<\/i>, <b>23<\/b>, 704\u2013708 (2018).","DOI":"10.1080\/1354750X.2018.1485054"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58) Reichart D, Lindberg EL, Maatz H, <i>et al.<\/i> Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. <i>Science<\/i>, <b>377<\/b>, eabo1984 (2022).","DOI":"10.1093\/eurheartj\/ehac544.2992"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59) Koenig AL, Shchukina I, Amrute J, Andhey PS, Zaitsev K, Lai L, Bajpai G, Bredemeyer A, Smith G, Jones C, Terrebonne E, Rentschler SL, Artyomov MN, Lavine KJ. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. <i>Nat. Cardiovasc. Res.<\/i>, <b>1<\/b>, 263\u2013280 (2022).","DOI":"10.1038\/s44161-022-00028-6"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60) Altman NL, Gill EA, Kahwash R, <i>et al.<\/i> Heart rate reduction is associated with reverse left ventricular remodeling and mechanism-specific molecular phenotypes in dilated cardiomyopathy. <i>Circ. Heart Fail.<\/i>, <b>18<\/b>, e012484 (2025).","DOI":"10.1161\/CIRCHEARTFAILURE.124.012484"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61) Galindo CL, Ryzhov S, Sawyer DB. Neuregulin as a heart failure therapy and mediator of reverse remodeling. <i>Curr. Heart Fail. Rep.<\/i>, <b>11<\/b>, 40\u201349 (2014).","DOI":"10.1007\/s11897-013-0176-2"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/1\/49_b25-00481\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T03:23:13Z","timestamp":1767410593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/1\/49_b25-00481\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b25-00481","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]},"article-number":"b25-00481"}}