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Herein, we explored the potential beneficial effects of treatment with siRNA AP-1 on pulmonary arterial hypertension (PAH), right ventricular dysfunction along with perivascular and interstitial fibrosis in pulmonary artery-PA, right ventricle-RV and lung in an experimental animal model of monocrotaline (MCT)-induced PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Golden Syrian hamsters were divided into: (1) C group-healthy animals taken as control; (2) MCT group obtained by a single subcutaneous injection of 60\u00a0mg\/kg MCT at the beginning of the experiment; (3) MCT-siRNA AP-1 group received a one-time subcutaneous dose of MCT and subcutaneous injections containing 100\u00a0nM siRNA AP-1, every two weeks. All animal groups received water and standard chow ad libitum for 12\u00a0weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In comparison with the MCT group, siRNA AP-1 treatment had significant beneficial effects on investigated tissues contributing to: (1) a reduction in TGF-\u03b21\/ET-1\/IL-1\u03b2\/TNF-\u03b1 plasma concentrations; (2) a reduced level of cytosolic ROS production in PA, RV and lung and notable improvements regarding the ultrastructure of these tissues; a decrease of inflammatory and fibrotic marker expressions in PA (COL1A\/Fibronectin\/Vimentin\/\u03b1-SMA\/CTGF\/Calponin\/MMP-9), RV and lung (COL1A\/CTGF\/Fibronectin\/\u03b1-SMA\/F-actin\/OB-cadherin) and an increase of endothelial marker expressions (CD31\/VE-cadherin) in PA; (4) structural and functional recoveries of the PA [reduced Vel, restored vascular reactivity (NA contraction, ACh relaxation)] and RV (enlarged internal cavity diameter in diastole, increased TAPSE and PRVOFs) associated with a decrease in systolic and diastolic blood pressure, and heart rate; (5) a reduced protein expression profile of AP-1S3\/ pFAK\/FAK\/pERK\/ERK and a significant decrease in the expression levels of miRNA-145, miRNA-210, miRNA-21, and miRNA-214 along with an increase of miRNA-124 and miRNA-204.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The siRNA AP-1-based therapy led to an improvement of pulmonary arterial and right ventricular function accompanied by a regression of perivascular and interstitial fibrosis in PA, RV and lung and a down-regulation of key inflammatory and fibrotic markers in MCT-treated hamsters.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-024-04933-1","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T14:02:09Z","timestamp":1707141729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The siRNA-mediated knockdown of AP-1 restores the function of the pulmonary artery and the right ventricle by reducing perivascular and interstitial fibrosis and key molecular players in cardiopulmonary disease"],"prefix":"10.1186","volume":"22","author":[{"given":"Ioana Karla","family":"Comari\u021ba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Tanko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliu\u021b\u0103 Lauren\u021biu","family":"Anghelache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-1745","authenticated-orcid":false,"given":"Adriana","family":"Georgescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"4933_CR1","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1016\/j.jacc.2009.04.012","volume":"54","author":"G Simonneau","year":"2009","unstructured":"Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al. 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