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Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Left ventricular (LV) remodeling consists in maladaptive changes in cardiac geometry and function following an insult such as ST-segment elevation myocardial infarction (STEMI). Interventions able to prevent LV remodeling after a STEMI are expected to improve the outcome of this condition. Paroxetine has inhibitory effects on GRK2, also known as beta-adrenergic receptor kinase 1 (ADRBK1). This drug does not yield beneficial effects on LV remodeling in patients with STEMI and LV ejection fraction \u2264 45%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared the molecular effects of paroxetine and drugs for neurohormonal antagonism (beta-blockers, angiotensin converting enzyme inhibitors\/angiotensin receptor blockers, mineralocorticoid receptor antagonists), using a bioinformatic approach integrating transcriptomic data in a swine model of post-MI and available evidence from the literature and massive public databases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among standard therapies for MI, beta-blockers are the only ones acting directly upon GKR2, but the mechanism of action overlaps with angiotensin-converting enzyme inhibitors\/angiotensin receptor blockers with respect to the AT2R-mediated anti-hypertensive response. Moreover, beta-blockers could have anti-fibrotic and anti-inflammatory effects through the regulation of myocyte-specific enhancer factors, endothelins and chemokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The additive benefit of paroxetine on the background of the standard therapy for STEMI, which includes beta-blockers, is expected to be limited. Nonetheless, paroxetine becomes particularly interesting when a beta-blocker is contraindicated (for example, in hypotensive individuals) or poorly tolerated.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.887248","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T04:45:59Z","timestamp":1657514759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The Potential Anti-remodeling Effect of Paroxetine After Myocardial Infarction May Be Blunted by Beta-Blockers"],"prefix":"10.3389","volume":"9","author":[{"given":"Oriol","family":"Iborra-Egea","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Aimo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Martini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Galvez-Monton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Burchielli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Panichella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Passino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoni","family":"Bayes-Genis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/eurheartj\/ehx393","article-title":"2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European society of cardiology (ESC).","volume":"39","author":"Ibanez","year":"2018","journal-title":"Eur Heart J."},{"key":"B2","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.amjcard.2017.03.013","article-title":"Incidence and prognostic impact of heart failure hospitalization during follow-up after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction.","volume":"119","author":"Taniguchi","year":"2017","journal-title":"Am J Cardiol."},{"key":"B3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12929-017-0322-3","article-title":"Macrophage activation and polarization in post-infarction cardiac remodeling.","volume":"24","author":"Gombozhapova","year":"2017","journal-title":"J Biomed Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1001\/jamacardio.2021.2247","article-title":"Effect of paroxetine-mediated G-protein receptor kinase 2 inhibition vs placebo in patients with anterior myocardial infarction: a randomized clinical trial.","volume":"6","author":"Pilgrim","year":"2021","journal-title":"JAMA Cardiol."},{"key":"B5","doi-asserted-by":"crossref","first-page":"277ra31","DOI":"10.1126\/scitranslmed.aaa0154","article-title":"Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction.","volume":"7","author":"Schumacher","year":"2015","journal-title":"Sci Transl Med."},{"key":"B6","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":"B7","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2013update.","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"D711","DOI":"10.1093\/nar\/gky964","article-title":"ArrayExpress update - 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