Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism
Abstract Background Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) impr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-022-01680-4 |
| _version_ | 1811320826924892160 |
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| author | Jingyuan Chen Jun Luo Haihua Qiu Yi Tang Xiaojie Yang Yusi Chen Zilu Li Jiang Li |
| author_facet | Jingyuan Chen Jun Luo Haihua Qiu Yi Tang Xiaojie Yang Yusi Chen Zilu Li Jiang Li |
| author_sort | Jingyuan Chen |
| collection | DOAJ |
| description | Abstract Background Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. Methods ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit‐8 and 5‐ethynyl‐2'‐deoxyuridine5‐ethynyl‐2'‐deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. Results ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. Conclusion ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism. |
| first_indexed | 2024-04-13T13:07:32Z |
| format | Article |
| id | doaj.art-7ff7967ffeb44d308a5db9e4244a1a7d |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-13T13:07:32Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-7ff7967ffeb44d308a5db9e4244a1a7d2022-12-22T02:45:44ZengBMCLipids in Health and Disease1476-511X2022-08-0121111210.1186/s12944-022-01680-4Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanismJingyuan Chen0Jun Luo1Haihua Qiu2Yi Tang3Xiaojie Yang4Yusi Chen5Zilu Li6Jiang Li7Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityDepartment of Cardiology, Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Hunan Normal UniversityDepartment of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityDepartment of Cardiovascular Medicine, Second Xiangya Hospital of Central South UniversityAbstract Background Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. Methods ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit‐8 and 5‐ethynyl‐2'‐deoxyuridine5‐ethynyl‐2'‐deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. Results ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. Conclusion ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism.https://doi.org/10.1186/s12944-022-01680-4Pulmonary arterial hypertensionApolipoprotein A5Endoplasmic reticulum stressGlucose- regulated protein 78 |
| spellingShingle | Jingyuan Chen Jun Luo Haihua Qiu Yi Tang Xiaojie Yang Yusi Chen Zilu Li Jiang Li Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism Lipids in Health and Disease Pulmonary arterial hypertension Apolipoprotein A5 Endoplasmic reticulum stress Glucose- regulated protein 78 |
| title | Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism |
| title_full | Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism |
| title_fullStr | Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism |
| title_full_unstemmed | Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism |
| title_short | Apolipoprotein A5 ameliorates MCT induced pulmonary hypertension by inhibiting ER stress in a GRP78 dependent mechanism |
| title_sort | apolipoprotein a5 ameliorates mct induced pulmonary hypertension by inhibiting er stress in a grp78 dependent mechanism |
| topic | Pulmonary arterial hypertension Apolipoprotein A5 Endoplasmic reticulum stress Glucose- regulated protein 78 |
| url | https://doi.org/10.1186/s12944-022-01680-4 |
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