{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:02:56Z","timestamp":1787313776062,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro\u2014FAPERJ","award":["# E-26\/200.881\/2021"],"award-info":[{"award-number":["# E-26\/200.881\/2021"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014CNPq","award":["# E-26\/200.881\/2021"],"award-info":[{"award-number":["# E-26\/200.881\/2021"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014CAPES","award":["# E-26\/200.881\/2021"],"award-info":[{"award-number":["# E-26\/200.881\/2021"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014CAPES; Instituto Nacional de Ci\u00eancia e Tecnologia de F\u00e1rmacos e Medicamentos\u2014INCT-INOFAR","award":["# E-26\/200.881\/2021"],"award-info":[{"award-number":["# E-26\/200.881\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Mitogen-activated protein kinase (MAPK) signaling is strongly implicated in cardiovascular remodeling in pulmonary hypertension (PH) and right ventricle (RV) failure. The effects of a newly designed p38 inhibitor, LASSBio-1824, were investigated in experimentally induced PH. Male Wistar rats were exposed to hypoxia and SU5416 (SuHx), and normoxic rats were used as controls. Oral treatment was performed for 14 days with either vehicle or LASSBio-1824 (50 mg\/kg). Pulmonary vascular resistance and RV structure and function were assessed by echocardiography and catheterization. Histological, immunohistochemical and Western blot analysis of lung and RV were performed to investigate cardiovascular remodeling and inflammation. Treatment with LASSBio-1824 normalized vascular resistance by attenuating vessel muscularization and endothelial dysfunction. In the heart, treatment decreased RV systolic pressure, hypertrophy and collagen content, improving cardiac function. Protein content of TNF-\u03b1, iNOS, phosphorylated p38 and caspase-3 were reduced both in lung vessels and RV tissues after treatment and a reduced activation of transcription factor c-fos was found in cardiomyocytes of treated SuHx rats. Therefore, LASSBio-1824 represents a potential candidate for remodeling-targeted treatment of PH.<\/jats:p>","DOI":"10.3390\/ph15070900","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T22:38:50Z","timestamp":1658443130000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel p38 Mitogen-Activated Protein Kinase Inhibitor Reverses Hypoxia-Induced Pulmonary Arterial Hypertension in Rats"],"prefix":"10.3390","volume":"15","author":[{"given":"Grazielle Fernandes","family":"Silva","sequence":"first","affiliation":[{"name":"Programa de Pesquisa em Desenvolvimento de F\u00e1rmacos, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Cardiologia, Instituto do Cora\u00e7\u00e3o Edson Saad, Universidade Federal do Rio de Janeiro, Rio de Janeiro 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