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The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension
We found previously that KLF4 expression was up‐regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS‐induced pulmon...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812256/ https://www.ncbi.nlm.nih.gov/pubmed/33342082 http://dx.doi.org/10.1111/jcmm.16194 |
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author | Sun, Desheng Ding, DanDan Li, Qinghai Xie, Min Xu, Yongjian Liu, Xiansheng |
author_facet | Sun, Desheng Ding, DanDan Li, Qinghai Xie, Min Xu, Yongjian Liu, Xiansheng |
author_sort | Sun, Desheng |
collection | PubMed |
description | We found previously that KLF4 expression was up‐regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS‐induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno‐associated virus 1 (AAV1)‐KLF4‐shRNA in vivo in rat model. The preventive and therapeutic effects were observed according to the different time‐point of AAV1‐KLF4‐shRNA 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‐induced PH model. While in the prevention group (AAV1‐KLF4‐shRNA 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‐induced PH and determined gene transfer of KLF4‐shRNA could prevent and ameliorate the progression of PH. |
format | Online Article Text |
id | pubmed-7812256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78122562021-01-22 The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension Sun, Desheng Ding, DanDan Li, Qinghai Xie, Min Xu, Yongjian Liu, Xiansheng J Cell Mol Med Original Articles We found previously that KLF4 expression was up‐regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS‐induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno‐associated virus 1 (AAV1)‐KLF4‐shRNA in vivo in rat model. The preventive and therapeutic effects were observed according to the different time‐point of AAV1‐KLF4‐shRNA 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‐induced PH model. While in the prevention group (AAV1‐KLF4‐shRNA 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‐induced PH and determined gene transfer of KLF4‐shRNA could prevent and ameliorate the progression of PH. John Wiley and Sons Inc. 2020-12-20 2021-01 /pmc/articles/PMC7812256/ /pubmed/33342082 http://dx.doi.org/10.1111/jcmm.16194 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Sun, Desheng Ding, DanDan Li, Qinghai Xie, Min Xu, Yongjian Liu, Xiansheng The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension |
title | The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension |
title_full | The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension |
title_fullStr | The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension |
title_full_unstemmed | The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension |
title_short | The preventive and therapeutic effects of AAV1‐KLF4‐shRNA in cigarette smoke‐induced pulmonary hypertension |
title_sort | preventive and therapeutic effects of aav1‐klf4‐shrna in cigarette smoke‐induced pulmonary hypertension |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812256/ https://www.ncbi.nlm.nih.gov/pubmed/33342082 http://dx.doi.org/10.1111/jcmm.16194 |
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