{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T18:27:33Z","timestamp":1776882453320,"version":"3.51.2"},"reference-count":81,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007385","name":"Cassa di Risparmio di Bologna","doi-asserted-by":"publisher","award":["19911"],"award-info":[{"award-number":["19911"]}],"id":[{"id":"10.13039\/100007385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phospholipase C (PLC) enzymes represent crucial participants in the plasma membrane of mammalian cells, including the cardiac sarcolemmal (SL) membrane of cardiomyocytes. They are responsible for the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) into 1,2-diacylglycerol (DAG) and inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), both essential lipid mediators. These second messengers regulate the intracellular calcium (Ca2+) concentration, which activates signal transduction cascades involved in the regulation of cardiomyocyte activity. Of note, emerging evidence suggests that changes in cardiomyocytes\u2019 phospholipid profiles are associated with an increased occurrence of cardiovascular diseases, but the underlying mechanisms are still poorly understood. This review aims to provide a comprehensive overview of the significant impact of PLC on the cardiovascular system, encompassing both physiological and pathological conditions. Specifically, it focuses on the relevance of PLC\u03b2 isoforms as potential cardiac biomarkers, due to their implications for pathological disorders, such as cardiac hypertrophy, diabetic cardiomyopathy, and myocardial ischemia\/reperfusion injury. Gaining a deeper understanding of the mechanisms underlying PLC\u03b2 activation and regulation is crucial for unraveling the complex signaling networks involved in healthy and diseased myocardium. Ultimately, this knowledge holds significant promise for advancing the development of potential therapeutic strategies that can effectively target and address cardiac disorders by focusing on the PLC\u03b2 subfamily.<\/jats:p>","DOI":"10.3390\/ijms241713096","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:25:24Z","timestamp":1692775524000},"page":"13096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Emerging Roles of Phospholipase C Beta Isozymes as Potential Biomarkers in Cardiac Disorders"],"prefix":"10.3390","volume":"24","author":[{"given":"Antonietta","family":"Fazio","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-9540","authenticated-orcid":false,"given":"Camilla","family":"Evangelisti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Cappellini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Mongiorgi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1599-686X","authenticated-orcid":false,"given":"Foteini-Dionysia","family":"Koufi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6543-8391","authenticated-orcid":false,"given":"Maria Vittoria","family":"Marvi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Torino, 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-5296","authenticated-orcid":false,"given":"Alessandra","family":"Ghigo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Torino, 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Manzoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7757-4000","authenticated-orcid":false,"given":"Roberta","family":"Fiume","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-5345","authenticated-orcid":false,"given":"Stefano","family":"Ratti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s10974-019-09539-5","article-title":"Cardiomyocyte damage control in heart failure and the role of the sarcolemma","volume":"40","author":"Kitmitto","year":"2019","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1111\/bph.13552","article-title":"Sarcolemmal dependence of cardiac protection and stress-resistance: Roles in aged or diseased hearts","volume":"173","author":"May","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pistritu, D.V., Vasiliniuc, A.C., Vasiliu, A., Visinescu, E.F., Visoiu, I.E., Vizdei, S., Mart\u00ednez Anghel, P., Tanca, A., Bucur, O., and Liehn, E.A. (2023). Phospholipids, the Masters in the Shadows during Healing after Acute Myocardial Infarction. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098360"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jacbts.2019.01.009","article-title":"Cardiac Muscle Membrane Stabilization in Myocardial Reperfusion Injury","volume":"4","author":"Houang","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_5","first-page":"H242","article-title":"Redistribution of phosphatidylethanolamine and phosphatidylserine precedes reperfusion-induced apoptosis","volume":"274","author":"Maulik","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fazio, A., Owusu Obeng, E., Rusciano, I., Marvi, M.V., Zoli, M., Mongiorgi, S., Ramazzotti, G., Follo, M.Y., McCubrey, J.A., and Cocco, L. (2020). Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155297"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Owusu Obeng, E., Rusciano, I., Marvi, M.V., Fazio, A., Ratti, S., Follo, M.Y., Xian, J., Manzoli, L., Billi, A.M., and Mongiorgi, S. (2020). Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072581"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.bbrc.2018.07.155","article-title":"Regulation of actin assembly by PI(4,5)P2 and other inositol phospholipids: An update on possible mechanisms","volume":"506","author":"Janmey","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1194\/jlr.R057984","article-title":"Phosphoinositide-specific phospholipase C in health and disease","volume":"56","author":"Cocco","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1042\/EBC20200041","article-title":"Phosphatidylinositol(4,5)bisphosphate: Diverse functions at the plasma membrane","volume":"64","author":"Katan","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.pharmthera.2005.04.002","article-title":"Ins(1,4,5)P3 receptors and inositol phosphates in the heart-evolutionary artefacts or active signal transducers?","volume":"107","author":"Woodcock","year":"2005","journal-title":"Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fphar.2014.00035","article-title":"Calcium and IP3 dynamics in cardiac myocytes: Experimental and computational perspectives and approaches","volume":"5","author":"Hohendanner","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/BF01931491","article-title":"1,2-diacylglycerol content in myocardium from spontaneously hypertensive rats during the development of hypertension","volume":"85","author":"Kondo","year":"1990","journal-title":"Basic Res. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0008-6363(98)00187-4","article-title":"Ins(1,4,5)P3 and cardiac dysfunction","volume":"40","author":"Woodcock","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"782767","DOI":"10.3389\/fphys.2021.782767","article-title":"Phosphatidylinositol-4,5-Bisphosphate Binding to Amphiphysin-II Modulates T-Tubule Remodeling: Implications for Heart Failure","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1253\/jcj.56.142","article-title":"Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart","volume":"56","author":"Shoki","year":"1992","journal-title":"Jpn. Circ. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"H840","DOI":"10.1152\/ajpheart.00632.2019","article-title":"Gene therapy targeting cardiac phosphoinositide 3-kinase (p110\u03b1) attenuates cardiac remodeling in type 2 diabetes","volume":"318","author":"Prakoso","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1096\/fj.09-133983","article-title":"Gq-initiated cardiomyocyte hypertrophy is mediated by phospholipase Cbeta1b","volume":"23","author":"Filtz","year":"2009","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"H1328","DOI":"10.1152\/ajpheart.00847.2012","article-title":"Phospholipase C signaling tonically represses basal atrial natriuretic factor secretion from the atria of the heart","volume":"304","author":"Chang","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1096\/fj.07-102558","article-title":"The extreme C-terminal region of phospholipase Cbeta1 determines subcellular localization and function; the \u201cb\u201d splice variant mediates alpha1-adrenergic receptor responses in cardiomyocytes","volume":"22","author":"Grubb","year":"2008","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1111\/j.1582-4934.2009.00812.x","article-title":"Reciprocal regulation of transcription factors and PLC isozyme gene expression in adult cardiomyocytes","volume":"14","author":"Singal","year":"2010","journal-title":"J. Cell Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1146\/annurev-pharmtox-030620-104842","article-title":"Preventing and Treating Anthracycline Cardiotoxicity: New Insights","volume":"61","author":"Sawicki","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1582-4934.2006.tb00412.x","article-title":"Losartan attenuates phospholipase C isozyme gene expression in hypertrophied hearts due to volume overload","volume":"10","author":"Dent","year":"2006","journal-title":"J. Cell Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/sj.bjp.0702676","article-title":"Expression of immediate early genes, GATA-4, and Nkx-2.5 in adrenergic-induced cardiac hypertrophy and during regression in adult mice","volume":"127","author":"Saadane","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11010-009-0296-x","article-title":"Phospholipase Cbeta4 isozyme is expressed in human, rat, and murine heart left ventricles and in HL-1 cardiomyocytes","volume":"337","author":"Otaegui","year":"2010","journal-title":"Mol. Cell Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tappia, P.S., and Dhalla, N.S. (2022). Upregulation of Phospholipase C Gene Expression Due to Norepinephrine-Induced Hypertrophic Response. Cells, 11.","DOI":"10.3390\/cells11162488"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"H719","DOI":"10.1152\/ajpheart.01107.2003","article-title":"Phospholipase C gene expression, protein content, and activities in cardiac hypertrophy and heart failure due to volume overload","volume":"287","author":"Dent","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1161\/01.RES.87.12.1095","article-title":"Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C","volume":"87","author":"Kamp","year":"2000","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1006\/phrs.1999.0631","article-title":"Possible mechanism of cardioprotective effect of ischaemic preconditioning in isolated rat heart","volume":"41","author":"Sharma","year":"2000","journal-title":"Pharmacol. Res."},{"key":"ref_30","first-page":"H642","article-title":"Protein kinase C translocation and PKC-dependent protein phosphorylation during myocardial ischemia","volume":"276","author":"Albert","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4939-8672-9_3","article-title":"Phospholipases: An Overview","volume":"1835","author":"Aloulou","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev-physiol-030212-183750","article-title":"Mammalian phospholipase C","volume":"75","author":"Kadamur","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.bbrc.2012.06.079","article-title":"Cloning, tissue distribution and sub-cellular localisation of phospholipase C X-domain containing protein (PLCXD) isoforms","volume":"424","author":"Gellatly","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj2880001","article-title":"Inositol-lipid-specific phospholipase C isoenzymes and their differential regulation by receptors","volume":"288","author":"Cockcroft","year":"1992","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1074\/jbc.273.1.417","article-title":"Replacements of single basic amino acids in the pleckstrin homology domain of phospholipase C-delta1 alter the ligand binding, phospholipase activity, and interaction with the plasma membrane","volume":"273","author":"Yagisawa","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101065","DOI":"10.1016\/j.plipres.2020.101065","article-title":"Phospholipase C families: Common themes and versatility in physiology and pathology","volume":"80","author":"Katan","year":"2020","journal-title":"Prog. Lipid Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/978-3-030-12457-1_9","article-title":"Phospholipase C","volume":"1131","author":"Bill","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1124\/mol.113.087403","article-title":"Structural insights into phospholipase C-\u03b2 function","volume":"84","author":"Lyon","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s13238-010-0099-6","article-title":"Extensions of PDZ domains as important structural and functional elements","volume":"1","author":"Wang","year":"2010","journal-title":"Protein Cell"},{"key":"ref_40","first-page":"573","article-title":"Aortic constriction induces hypertension and cardiac hypertrophy via (pro)renin receptor activation and the PLC-\u03b23 signaling pathway","volume":"19","author":"Wu","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1021\/cr200209p","article-title":"Mechanism of activation and inactivation of Gq\/phospholipase C-\u03b2 signaling nodes","volume":"111","author":"Harden","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yjmcc.2015.04.016","article-title":"The atypical \u2018b\u2019 splice variant of phospholipase C\u03b21 promotes cardiac contractile dysfunction","volume":"84","author":"Grubb","year":"2015","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.yjmcc.2009.08.020","article-title":"Selective activation of the \u201cb\u201d splice variant of phospholipase Cbeta1 in chronically dilated human and mouse atria","volume":"47","author":"Woodcock","year":"2009","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dewing, J.M., Saunders, V., O\u2019Kelly, I., and Wilson, D.I. (2022). Defining cardiac cell populations and relative cellular composition of the early fetal human heart. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0259477"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1124\/mol.118.112524","article-title":"Small-Molecule G Protein-Coupled Receptor Kinase Inhibitors Attenuate G Protein-Coupled Receptor Kinase 2-Mediated Desensitization of Vasoconstrictor-Induced Arterial Contractions","volume":"94","author":"Rainbow","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.2174\/13816128113196660752","article-title":"Regulation of endothelial nitric oxide synthase activity by protein-protein interaction","volume":"20","author":"Su","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.CIR.97.9.892","article-title":"Expression of Gq alpha and PLC-beta in scar and border tissue in heart failure due to myocardial infarction","volume":"97","author":"Ju","year":"1998","journal-title":"Circulation"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1182\/blood-2004-05-2005","article-title":"The relative role of PLCbeta and PI3Kgamma in platelet activation","volume":"106","author":"Lian","year":"2005","journal-title":"Blood"},{"key":"ref_49","first-page":"785","article-title":"Thrombosis and platelets: An update","volume":"38","author":"Koupenova","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1182\/blood.V88.5.1684.1684","article-title":"Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function","volume":"88","author":"Lee","year":"1996","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1182\/blood.V88.5.1676.1676","article-title":"Human platelet signaling defect characterized by impaired production of inositol-1,4,5-triphosphate and phosphatidic acid and diminished Pleckstrin phosphorylation: Evidence for defective phospholipase C activation","volume":"88","author":"Yang","year":"1996","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrcardio.2016.25","article-title":"Epidemiology and aetiology of heart failure","volume":"13","author":"Ziaeian","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1172\/JCI24178","article-title":"Protein kinase cascades in the regulation of cardiac hypertrophy","volume":"115","author":"Dorn","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"37341","DOI":"10.1074\/jbc.M106572200","article-title":"Evidence for selective coupling of alpha 1-adrenergic receptors to phospholipase C-beta 1 in rat neonatal cardiomyocytes","volume":"276","author":"Arthur","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1034\/j.1600-0773.2001.d01-148.x","article-title":"Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced cardiomyopathy","volume":"89","author":"Khattab","year":"2001","journal-title":"Pharmacol. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S294","DOI":"10.1097\/00005344-199800001-00082","article-title":"Coordinated upregulation of the cardiac endothelin system in a rat model of heart failure","volume":"31","author":"Picard","year":"1998","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bcp.2015.01.014","article-title":"Protective effects of endothelin receptor A and B inhibitors against doxorubicin-induced cardiomyopathy","volume":"94","author":"Schwebe","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s11010-009-0061-1","article-title":"Regulation of c-Fos and c-Jun gene expression by phospholipase C activity in adult cardiomyocytes","volume":"327","author":"Singal","year":"2009","journal-title":"Mol. Cell Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/bbrc.2000.3255","article-title":"Differential regulation of phospholipase C-beta isozymes in cardiomyocyte hypertrophy","volume":"275","author":"Schnabel","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"146","DOI":"10.4093\/dmj.2020.0282","article-title":"Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes","volume":"45","author":"Park","year":"2021","journal-title":"Diabetes Metab. J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ghosh, N., Chacko, L., Bhattacharya, H., Vallamkondu, J., Nag, S., Dey, A., Karmakar, T., Reddy, P.H., Kandimalla, R., and Dewanjee, S. (2023). Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041126"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1006\/jmcc.1997.0576","article-title":"Impairment of the sarcolemmal phospholipase D-phosphatidate phosphohydrolase pathway in diabetic cardiomyopathy","volume":"30","author":"Williams","year":"1998","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/BF01908314","article-title":"Cardiac alpha- and beta-adrenergic receptor alterations in diabetic cardiomyopathy","volume":"77","author":"Heyliger","year":"1982","journal-title":"Basic. Res. Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1146\/annurev.biochem.70.1.281","article-title":"Regulation of phosphoinositide-specific phospholipase C","volume":"70","author":"Rhee","year":"2001","journal-title":"Annu. Rev. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1023\/B:MCBI.0000028756.31782.46","article-title":"Defective sarcolemmal phospholipase C signaling in diabetic cardiomyopathy","volume":"261","author":"Tappia","year":"2004","journal-title":"Mol. Cell Biochem."},{"key":"ref_66","first-page":"2051","article-title":"Current advances in the study of diabetic cardiomyopathy: From clinicopathological features to molecular therapeutics (Review)","volume":"20","author":"Sun","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1161\/CIRCHEARTFAILURE.108.765750","article-title":"Inhibition of protein kinase C-beta by ruboxistaurin preserves cardiac function and reduces extracellular matrix production in diabetic cardiomyopathy","volume":"2","author":"Connelly","year":"2009","journal-title":"Circ. Heart Fail."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1139\/Y10-019","article-title":"Phospholipase C as a potential target for cardioprotection during oxidative stress","volume":"88","author":"Tappia","year":"2010","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2014From mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3892\/etm.2022.11357","article-title":"Myocardial ischemia\/reperfusion injury: Mechanisms of injury and implications for management (Review)","volume":"23","author":"He","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"872","DOI":"10.3389\/fphar.2020.00872","article-title":"Targeting Calcium Homeostasis in Myocardial Ischemia\/Reperfusion Injury: An Overview of Regulatory Mechanisms and Therapeutic Reagents","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.yjmcc.2018.07.245","article-title":"Stimulation of P2Y11 receptor modulates cardiac fibroblasts secretome toward immunomodulatory and protective roles after Hypoxia\/Reoxygenation injury","volume":"121","author":"Lefort","year":"2018","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cardiores.2003.09.031","article-title":"Protein kinase activation and myocardial ischemia\/reperfusion injury","volume":"61","author":"Armstrong","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1161\/01.RES.76.2.261","article-title":"Inositol phosphate release and metabolism during myocardial ischemia and reperfusion in rat heart","volume":"76","author":"Anderson","year":"1995","journal-title":"Circ. Res."},{"key":"ref_75","first-page":"H877","article-title":"Role of phospholipases A2 and C in myocardial ischemic reperfusion injury","volume":"260","author":"Prasad","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0022-2828(91)90217-A","article-title":"Increased myocardial inositol trisphosphate levels during alpha 1-adrenergic stimulation and reperfusion of ischaemic rat heart","volume":"23","author":"Mouton","year":"1991","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0003-9861(02)00733-6","article-title":"Identification of the changes in phospholipase C isozymes in ischemic-reperfused rat heart","volume":"411","author":"Asemu","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H2598","DOI":"10.1152\/ajpheart.00506.2004","article-title":"Inhibition of PLC improves postischemic recovery in isolated rat heart","volume":"287","author":"Asemu","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1172\/JCI0213200","article-title":"Formation of protein kinase C(epsilon)-Lck signaling modules confers cardioprotection","volume":"109","author":"Ping","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1055\/s-2004-817978","article-title":"Protein kinase C and myocardial calcium handling during ischemia and reperfusion: Lessons learned using Rhod-2 spectrofluorometry","volume":"52","author":"Stamm","year":"2004","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105716","DOI":"10.1016\/j.phrs.2021.105716","article-title":"The roles of PKC-\u03b4 and PKC-\u03b5 in myocardial ischemia\/reperfusion injury","volume":"170","author":"Chen","year":"2021","journal-title":"Pharmacol. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13096\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:40:31Z","timestamp":1760128831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,23]]},"references-count":81,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713096"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713096","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,23]]}}}