Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat
IntroductionCurrent targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.859422/full |
| _version_ | 1811255918880358400 |
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| author | Lin Huang Huayang Li Suiqing Huang Shunjun Wang Quan Liu Li Luo Shuangjiao Gan Guangguo Fu PeiYun Zou Guangxian Chen Zhongkai Wu |
| author_facet | Lin Huang Huayang Li Suiqing Huang Shunjun Wang Quan Liu Li Luo Shuangjiao Gan Guangguo Fu PeiYun Zou Guangxian Chen Zhongkai Wu |
| author_sort | Lin Huang |
| collection | DOAJ |
| description | IntroductionCurrent targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of traditional Chinese medicine Qiang-Huo (Notopterygium incisum), had shown the antiproliferative and anti-inflammatory properties in previous studies, we hypothesized that it could play a role in ameliorating PAH.MethodsIn vivo, we conducted monocrotaline (MCT) induced PAH rats and treated them with notopterol for 3 weeks. Then, the rats were examined by echocardiography and RV catheterization. The heart and lung specimens were harvested for the detection of gross examination, histological examination and expression of inflammatory molecules. In vitro, human pulmonary arterial smooth muscle cells (HPASMCs) were treated with notopterol after hypoxia; then, cell proliferation was assessed by cell counting kit-8 and Edu assay, and cell migration was detected by wound healing assays.ResultsWe found that notopterol improved mortality rate and RV function while reducing right ventricular systolic pressure in MCT-induced PAH rats. Furthermore, notopterol reduced right ventricular hypertrophy and fibrosis, and it also eased pulmonary vascular remodeling and MCT-induced muscularization. In addition, notopterol attenuated the pro-inflammatory factor (IL-1β, IL-6) and PCNA in the lungs of PAH rats. For the cultured HPASMCs subjected to hypoxia, we found that notopterol can inhibit the proliferation and migration of HPASMCs.ConclusionOur studies show that notopterol exerts anti-inflammatory and anti-proliferative effects in the pulmonary arteries, which may contribute to prevention of PAH. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-12T17:32:14Z |
| publishDate | 2022-06-01 |
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| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-87beb43049994548836a1565b6df83c82022-12-22T03:23:06ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.859422859422Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in RatLin Huang0Huayang Li1Suiqing Huang2Shunjun Wang3Quan Liu4Li Luo5Shuangjiao Gan6Guangguo Fu7PeiYun Zou8Guangxian Chen9Zhongkai Wu10Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaGuangZhou Janus Biotechnology Co. Ltd., Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaIntroductionCurrent targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of traditional Chinese medicine Qiang-Huo (Notopterygium incisum), had shown the antiproliferative and anti-inflammatory properties in previous studies, we hypothesized that it could play a role in ameliorating PAH.MethodsIn vivo, we conducted monocrotaline (MCT) induced PAH rats and treated them with notopterol for 3 weeks. Then, the rats were examined by echocardiography and RV catheterization. The heart and lung specimens were harvested for the detection of gross examination, histological examination and expression of inflammatory molecules. In vitro, human pulmonary arterial smooth muscle cells (HPASMCs) were treated with notopterol after hypoxia; then, cell proliferation was assessed by cell counting kit-8 and Edu assay, and cell migration was detected by wound healing assays.ResultsWe found that notopterol improved mortality rate and RV function while reducing right ventricular systolic pressure in MCT-induced PAH rats. Furthermore, notopterol reduced right ventricular hypertrophy and fibrosis, and it also eased pulmonary vascular remodeling and MCT-induced muscularization. In addition, notopterol attenuated the pro-inflammatory factor (IL-1β, IL-6) and PCNA in the lungs of PAH rats. For the cultured HPASMCs subjected to hypoxia, we found that notopterol can inhibit the proliferation and migration of HPASMCs.ConclusionOur studies show that notopterol exerts anti-inflammatory and anti-proliferative effects in the pulmonary arteries, which may contribute to prevention of PAH.https://www.frontiersin.org/articles/10.3389/fcvm.2022.859422/fullpulmonary arterial hypertensionnotopterolpulmonary vascular remodelinginflammationpulmonary arterial smooth muscular cell |
| spellingShingle | Lin Huang Huayang Li Suiqing Huang Shunjun Wang Quan Liu Li Luo Shuangjiao Gan Guangguo Fu PeiYun Zou Guangxian Chen Zhongkai Wu Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat Frontiers in Cardiovascular Medicine pulmonary arterial hypertension notopterol pulmonary vascular remodeling inflammation pulmonary arterial smooth muscular cell |
| title | Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat |
| title_full | Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat |
| title_fullStr | Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat |
| title_full_unstemmed | Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat |
| title_short | Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat |
| title_sort | notopterol attenuates monocrotaline induced pulmonary arterial hypertension in rat |
| topic | pulmonary arterial hypertension notopterol pulmonary vascular remodeling inflammation pulmonary arterial smooth muscular cell |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.859422/full |
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