{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:24:10Z","timestamp":1789986250413,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research &amp; Innovation, Ministry of Education, Saudi Arabia","award":["IFKSUDR_H150"],"award-info":[{"award-number":["IFKSUDR_H150"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathological cardiac remodeling is associated with cardiovascular disease and can lead to heart failure. Nuclear factor-kappa B (NF-\u03baB) is upregulated in the hypertrophic heart. Moreover, the expression of the G-protein-coupled receptor kinase 2 (GRK2) is increased and linked to the progression of heart failure. The inhibitory effects of paroxetine on GRK2 have been established. However, its protective effect on I\u03baB\u03b1\/NF\u03baB signaling has not been elucidated. This study investigated the cardioprotective effect of paroxetine in an animal model of cardiac hypertrophy (CH), focusing on its effect on GRK2-mediated NF-\u03baB-regulated expression of prohypertrophic and profibrotic genes. Wistar albino rats were administered normal saline, paroxetine, or fluoxetine, followed by isoproterenol to induce CH. The cardioprotective effects of the treatments were determined by assessing cardiac injury, inflammatory biomarker levels, histopathological changes, and hypertrophic and fibrotic genes in cardiomyocytes. Paroxetine pre-treatment significantly decreased the HW\/BW ratio (p &lt; 0.001), and the expression of prohypertrophic and profibrotic genes Troponin-I (p &lt; 0.001), BNP (p &lt; 0.01), ANP (p &lt; 0.001), hydroxyproline (p &lt; 0.05), TGF-\u03b21 (p &lt; 0.05), and \u03b1SMA (p &lt; 0.01) as well as inflammatory markers. It also markedly decreased pI\u03baB\u03b1, NF\u03baB(p105) subunit expression (p &lt; 0.05) and phosphorylation. The findings suggest that paroxetine prevents pathological cardiac remodeling by inhibiting the GRK2-mediated I\u03baB\u03b1\/NF-\u03baB signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms242417270","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T08:47:26Z","timestamp":1702025246000},"page":"17270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-\u03baB Mediated Prohypertrophic and Profibrotic Gene Expression"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3367-002X","authenticated-orcid":false,"given":"Asma S.","family":"Alonazi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-414X","authenticated-orcid":false,"given":"Anfal F.","family":"Bin Dayel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danah A.","family":"Albuaijan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alhanouf S.","family":"Bin Osfur","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemah M.","family":"Hakami","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaden S.","family":"Alzayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad R.","family":"Almotairi","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad R.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana M.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-0840","authenticated-orcid":false,"given":"Maha A.","family":"Alamin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2369-2461","authenticated-orcid":false,"given":"Hanan K.","family":"Alghibiwi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5283-1576","authenticated-orcid":false,"given":"Nouf M.","family":"Alrasheed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled A.","family":"Alhosaini","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, October 29). Cardiovascular Diseases; WHO. June 2021, Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1016\/j.jacc.2020.11.021","article-title":"The Global Burden of Cardiovascular Diseases and Risks: A Compass for Global Action","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1042\/CS20171167","article-title":"Mechanisms contributing to cardiac remodelling","volume":"131","author":"Wu","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10557-017-6719-0","article-title":"Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis","volume":"31","author":"Wu","year":"2017","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1161\/01.CIR.0000120390.68287.BB","article-title":"Hypertrophy of the Heart","volume":"109","author":"Frey","year":"2004","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1111\/jcmm.14129","article-title":"Molecular biomarkers in cardiac hypertrophy","volume":"23","author":"Zhu","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.12659\/MSMBR.900437","article-title":"Cardiac Hypertrophy: An Introduction to Molecular and Cellular Basis","volume":"22","author":"Samak","year":"2016","journal-title":"Med. Sci. Monit. Basic Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yjmcc.2016.06.001","article-title":"Physiological and pathological cardiac hypertrophy","volume":"97","author":"Shimizu","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.peptides.2018.05.012","article-title":"Atrial and brain natriuretic peptides: Hormones secreted from the heart","volume":"111","author":"Nakagawa","year":"2019","journal-title":"Peptides"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1440-1681.2007.04585.x","article-title":"Differences between Pathological and Physiological Cardiac Hypertrophy: Novel Therapeutic Strategies to Treat Heart Failure","volume":"34","author":"McMullen","year":"2007","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.bbadis.2016.11.006","article-title":"The role of \u03b1-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling","volume":"1863","author":"Shinde","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","article-title":"Cardiac Fibrosis: The Fibroblast Awakens","volume":"118","author":"Travers","year":"2016","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/cvr\/cvaa324","article-title":"Cardiac fibrosis","volume":"117","author":"Frangogiannis","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_15","first-page":"157","article-title":"Do multiple nuclear factor kappa B activation mechanisms explain its varied effects in the heart?","volume":"13","author":"Kumar","year":"2013","journal-title":"Ochsner J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fphar.2019.00112","article-title":"G Protein-Coupled Receptor Kinase 2 (GRK2) as a Potential Therapeutic Target in Cardiovascular and Metabolic Diseases","volume":"10","author":"Murga","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mayor, F., and Murga, C. (2022). G Protein-Coupled Receptor Kinases Take Central Stage. Cells, 12.","DOI":"10.3390\/cells12010023"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1152\/physrev.00015.2014","article-title":"The Evolving Impact of G Protein-Coupled Receptor Kinases in Cardiac Health and Disease","volume":"95","author":"Sato","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bencivenga, L., Palaia, M.E., Sepe, I., Gambino, G., Komici, K., Cannavo, A., Femminella, G.D., and Rengo, G. (2021). Why Do We Not Assess Sympathetic Nervous System Activity in Heart Failure Management: Might GRK2 Serve as a New Biomarker?. Cells, 10.","DOI":"10.3390\/cells10020457"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Schlegel, P., Reinkober, J., Meinhardt, E., Tscheschner, H., Gao, E., Schumacher, S.M., Yuan, A., Backs, J., Most, P., and Wieland, T. (2017). G protein-coupled receptor kinase 2 promotes cardiac hypertrophy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182110"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Umbarkar, P., Ejantkar, S., Tousif, S., and Lal, H. (2021). Mechanisms of Fibroblast Activation and Myocardial Fibrosis: Lessons Learned from FB-Specific Conditional Mouse Models. Cells, 10.","DOI":"10.3390\/cells10092412"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kowalska, M., Nowaczyk, J., Fija\u0142kowski, \u0141., and Nowaczyk, A. (2021). Paroxetine\u2014Overview of the Molecular Mechanisms of Action. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041662"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kosi\u0107, M., Ne\u0161i\u0107, Z., Glumac, S., Vasi\u0107, M., Pajovi\u0107, V., Savi\u0107, B., and Japund\u017ei\u0107-\u017digon, N. (2022). Paroxetine mitigates cardiac remodelling by doxorubicin and increases survival. Biomed. Pharmacother., 145.","DOI":"10.1016\/j.biopha.2021.112411"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1021\/cb3003013","article-title":"Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility","volume":"7","author":"Thal","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.2147\/NDT.S109880","article-title":"Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction","volume":"12","author":"Tian","year":"2016","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1124\/mol.113.089631","article-title":"Structural and Functional Analysis of G Protein\u2013Coupled Receptor Kinase Inhibition by Paroxetine and a Rationally Designed Analog","volume":"85","author":"Kristoff","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1021\/acs.jmedchem.7b00112","article-title":"Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine","volume":"60","author":"Waldschmidt","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e016364","DOI":"10.1161\/JAHA.120.016364","article-title":"Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension","volume":"10","author":"Sun","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1016\/j.cardfail.2015.06.318","article-title":"Paroxetine-Mediated GRK2 Inhibition Reverses Cardiac Dysfunction and Remodeling After Myocardial Infarction","volume":"21","author":"Schumacher","year":"2015","journal-title":"J. Card. Fail."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/eci.12598","article-title":"\u03b2-adrenergic receptor signalling and its functional consequences in the diseased heart","volume":"46","author":"Najafi","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H2410","DOI":"10.1152\/ajpheart.2001.281.6.H2410","article-title":"Isoproterenol-induced cardiac hypertrophy: Role of circulatory versus cardiac renin-angiotensin system","volume":"281","author":"Leenen","year":"2001","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S1734-1140(09)70143-4","article-title":"Chronic \u03b2-adrenergic activation-induced left ventricular systolic dysfunction is associated with systemic release of TNF-\u03b1 and IL-1-\u03b2 in rats","volume":"61","author":"Kumar","year":"2009","journal-title":"Pharmacol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3109\/15376516.2015.1128035","article-title":"Effect of aliskiren and carvedilol on expression of Ca2+\/calmodulin-dependent protein kinase II \u03b4-subunit isoforms in cardiac hypertrophy rat model","volume":"26","author":"Fadda","year":"2016","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/cvr\/cvs249","article-title":"\u03b2-Adrenergic receptor stimulation causes cardiac hypertrophy via a G\u03b2\u03b3\/Erk-dependent pathway","volume":"96","author":"Vidal","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/aps.2010.231","article-title":"Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression","volume":"32","author":"Guo","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_36","first-page":"230","article-title":"Isoproterenol-induced heart failure in rat heart: Evaluation and cardioprotective strategy","volume":"11","author":"Bourdier","year":"2019","journal-title":"Arch. Cardiovasc. Dis. Suppl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"822345","DOI":"10.3389\/fimmu.2021.822345","article-title":"G Protein-coupled receptor kinase 2 as novel therapeutic target in fibrotic diseases","volume":"12","author":"Li","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s12265-015-9646-0","article-title":"Integrating GRK2 and NFkappaB in the pathophysiology of cardiac hypertrophy","volume":"8","author":"Sorriento","year":"2015","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.jacc.2017.06.049","article-title":"Pharmacological and activated fibroblast targeting of G\u03b2\u03b3-GRK2 after myocardial ischemia attenuates heart failure progression","volume":"70","author":"Travers","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/14728222.2019.1575363","article-title":"GRK2 and GRK5 as therapeutic targets and their role in maladaptive and pathological cardiac hypertrophy","volume":"23","author":"Lieu","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/bs.ai.2017.05.003","article-title":"G protein-coupled receptor kinases in the inflammatory response and signaling","volume":"136","author":"Steury","year":"2017","journal-title":"Adv. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"38.15","DOI":"10.4049\/jimmunol.182.Supp.38.15","article-title":"G-Protein coupled receptor kinases mediate TNF alpha-induced NF kappaB signaling via direct interaction with and phosphorylation of I kappa B alpha (38.15)","volume":"182","author":"Patial","year":"2009","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1124\/mol.116.107698","article-title":"GRK2 mediates arginine vasopressin-induced interleukin-6 production via nuclear factor-\u03baB signaling neonatal rat cardiac fibroblast","volume":"92","author":"Xu","year":"2017","journal-title":"Mol. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/CIRCRESAHA.116.309538","article-title":"Cardiac fibroblast GRK2 deletion enhances contractility and remodeling following ischemia\/reperfusion injury","volume":"119","author":"Woodall","year":"2016","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/1440-1681.12696","article-title":"GRK2\/\u03b2-arrestin mediates arginine vasopressin-induced cardiac fibroblast proliferation","volume":"44","author":"Chen","year":"2017","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhou, W.-W., Sun, J.-H., Yang, H.-X., Xu, G.-R., Zhang, Y., Song, Q.-H., Zhang, C., Liu, W.-Z., and Liu, X.-C. (2021). Modified citrus pectin prevents isoproterenol-induced cardiac hypertrophy associated with p38 signalling and TLR4\/JAK\/STAT3 pathway. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112178"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"380","DOI":"10.12659\/MSMBR.907162","article-title":"Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet","volume":"23","author":"Goncalves","year":"2017","journal-title":"Med. Sci. Monit. Basic Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s11010-017-3253-0","article-title":"Apocynin prevents isoproterenol-induced cardiac hypertrophy in rat","volume":"445","author":"Saleem","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.2147\/DDDT.S109287","article-title":"Sitagliptin attenuates cardiomyopathy by modulating the JAK\/STAT signaling pathway in experimental diabetic rats","volume":"10","author":"Hasan","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Crowe, A.R., and Yue, W. (2019). Semi-quantitative Determination of Protein Expression using Immunohistochemistry Staining and Analysis: An Integrated Protocol. Bio Protoc., 9.","DOI":"10.21769\/BioProtoc.3465"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1080\/21655979.2022.2033380","article-title":"MicroRNA-130a attenuates cardiac fibrosis after myocardial infarction through TGF-\u03b2\/Smad signaling by directly targeting TGF-\u03b2 receptor 1","volume":"13","author":"Feng","year":"2022","journal-title":"Bioengineered"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104117","DOI":"10.1016\/j.dib.2019.104117","article-title":"Data on changes of NF-\u03baB gene expression in liver and lungs as a biomarker and hepatic injury in CLP-induced septic rats","volume":"25","author":"Miri","year":"2019","journal-title":"Data Brief"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Peinnequin, A., Mouret, C., Birot, O., Alonso, A., Mathieu, J., Claren\u00e7on, D., Agay, D., Chancerelle, Y., and Multon, E. (2004). Rat pro-inflammatory cytokine and cytokine related mRNA quantification by real-time polymerase chain reaction using SYBR green. BMC Immunol., 5.","DOI":"10.1186\/1471-2172-5-3"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1006\/jmcc.2000.1215","article-title":"CTGF expression is induced by TGF- beta in cardiac fibroblasts and cardiac myocytes: A potential role in heart fibrosis","volume":"32","author":"Chen","year":"2000","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"272","DOI":"10.21037\/cdt.2019.06.01","article-title":"Effect of paeoniflorin on cardiac remodeling in chronic heart failure rats through the transforming growth factor \u03b21\/Smad signaling pathway","volume":"9","author":"Liu","year":"2019","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.biopha.2018.01.138","article-title":"Icariside II attenuates myocardial fibrosis by inhibiting nuclear factor-\u03baB and the TGF-\u03b21\/Smad2 signalling pathway in spontaneously hypertensive rats","volume":"100","author":"Fu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fiordelisi, A., Iaccarino, G., Morisco, C., Coscioni, E., and Sorriento, D. (2019). NFkappaB is a Key Player in the Crosstalk between Inflammation and Cardiovascular Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071599"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:35:41Z","timestamp":1760132141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,8]]},"references-count":58,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242417270"],"URL":"https:\/\/doi.org\/10.3390\/ijms242417270","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,8]]}}}