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Here, we aim to investigate whether CS\u2010induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno\u2010associated virus 1 (AAV1)\u2010KLF4\u2010shRNA in vivo <jats:italic>in rat model<\/jats:italic>. The preventive and therapeutic effects were observed according to the different time\u2010point of AAV1\u2010KLF4\u2010shRNA intratracheal administration. We tested haemodynamic measurements of systemic and pulmonary circulations and observed the degree of pulmonary vascular remodelling. In the preventive experiment, KLF4 expression and some pulmonary circulation hemodynamic measurements such as right ventricular systolic pressure (RVSP), mean right ventricular pressure (mRVP), peak RV pressure rate of rise (dP\/dt max) and right ventricle (RV) contractility index were increased significantly in the CS\u2010induced PH model. While in the prevention group (AAV1\u2010KLF4\u2010shRNA group), RVSP, mRVP, dP\/dt max and RV contractility index which are associated with systolic function of right ventricle decreased and the degree of pulmonary vascular remodelling relieved. In the therapeutic experiment, we observed a similar trend. Our findings emphasize the feasibility of sustained pulmonary vascular KLF4 gene knockdown using intratracheal delivery of AAV1 in an animal model of cigarette smoke\u2010induced PH and determined gene transfer of KLF4\u2010shRNA could prevent and ameliorate the progression of PH.<\/jats:p>","DOI":"10.1111\/jcmm.16194","type":"journal-article","created":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T16:06:22Z","timestamp":1608480382000},"page":"1238-1251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The preventive and therapeutic effects of AAV1\u2010KLF4\u2010shRNA in cigarette smoke\u2010induced pulmonary hypertension"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-5101","authenticated-orcid":false,"given":"Desheng","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Key Laboratory of Pulmonary Diseases 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