{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:54:42Z","timestamp":1778738082934,"version":"3.51.4"},"reference-count":71,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secretariat of Science, Humanities, Technology, and Innovation (SECTEI), Mexico City","award":["813967"],"award-info":[{"award-number":["813967"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We evaluated the effects of fenofibrate (FF) in a SU5416\/hypoxia model of pulmonary arterial hypertension (PAH) with a specific focus on its influence on the renin\u2013angiotensin system (RAS). We assessed right ventricular systolic pressure (RVSP), mean pulmonary artery pressure (mPAP), medial pulmonary artery wall thickening, right ventricular (RV) hypertrophy, systolic pulmonary artery pressure (SPAP), pulmonary artery effective elastance (PAEa), RV diastolic pressure (RVDP), RV developed pressure (RVDevP), right ventricular\u2013pulmonary arterial coupling index (RVPAC), RV dp\/dt max and dp\/dt min. Levels of angiotensin II, angiotensin (1\u20137), angiotensin-converting enzyme 2 (ACE2), Bmpr2, Smad5 and nitrite (NO2\u2212) and nitrate (NO3\u2212) in the lung and RV were evaluated. The expression of AT1R, MAS receptors, and ACE2 in lung tissue was assessed. FF prevented the increase in RVSP, mPAP, RV hypertrophy, reduced pulmonary arterioles remodeling, and attenuated the rise in SPAP, mPAP, and PAEa. In the RV, it reduced RVDevP and prevented the decrease in dp\/dt min, without affecting RVDP. RVPAC showed partial improvement. In lung tissue, FF decreased angiotensin II levels, the Ang II\/Ang-(1\u20137) ratio, and reduced angiotensin II receptor type 1 (AT1R) expression, while preserving the receptor for the angiotensin-(1\u20137) (MAS) and ACE2. FF tended to restore Bmpr2\/Smad5 expression. NO2\u2212 levels were preserved and tended to preserve (NO3\u2212) levels. In the RV, Ang-(1\u20137) increased, ACE2 was preserved, and NO2\u2212 and NO3 levels were maintained. FF exerts protective effects in Su\/Hx-induced PAH.<\/jats:p>","DOI":"10.3390\/ijms262110251","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T01:14:02Z","timestamp":1761182042000},"page":"10251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fenofibrate as a Modulator of the Renin\u2013Angiotensin System in Su\/Hx-Induced Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-431X","authenticated-orcid":false,"given":"Karla M.","family":"Rada-Pascual","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"},{"name":"Secci\u00f3n de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0522-9395","authenticated-orcid":false,"given":"Alejandra M.","family":"Z\u00faniga-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamnia Q.","family":"Alvarez-Alvarez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"},{"name":"Secci\u00f3n de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-1050","authenticated-orcid":false,"given":"Leonardo","family":"Del Valle-Mondrag\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda \u201cDr. Rafael M\u00e9ndez Mart\u00ednez\u201d, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8315-8572","authenticated-orcid":false,"given":"Ivan","family":"Rubio-Gayosso","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-7695","authenticated-orcid":false,"given":"Constanza E.","family":"Mart\u00ednez-Olivares","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Patolog\u00eda Experimental, Departamento de Patolog\u00eda, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n \u201cSalvador Zubir\u00e1n\u201d, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-3833","authenticated-orcid":false,"given":"Rogelio","family":"Hern\u00e1ndez-Pando","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Patolog\u00eda Experimental, Departamento de Patolog\u00eda, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n \u201cSalvador Zubir\u00e1n\u201d, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-4202","authenticated-orcid":false,"given":"Horacio","family":"Osorio-Alonso","sequence":"additional","affiliation":[{"name":"Departamento de Fisiopatolog\u00eda Cardio-Renal, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2077-7007","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"S\u00e1nchez-Gloria","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-6223","authenticated-orcid":false,"given":"Pedro L.","family":"Flores","sequence":"additional","affiliation":[{"name":"Departamento de Instrumentaci\u00f3n Electromec\u00e1nica, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6825-3600","authenticated-orcid":false,"given":"Julio","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-2420","authenticated-orcid":false,"given":"Jaime H.","family":"G\u00f3mez-Zamudio","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Bioqu\u00edmica, Hospital de Especialidades \u201cBernardo Sepulveda\u201d, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-398X","authenticated-orcid":false,"given":"Roxana","family":"Carb\u00f3","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-1632","authenticated-orcid":false,"given":"Fausto","family":"S\u00e1nchez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1055\/s-0033-1356496","article-title":"Pathology and pathobiology of pulmonary hypertension","volume":"34","author":"Guignabert","year":"2013","journal-title":"Semin. 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