Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II
Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2017-05-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320317706653 |
| _version_ | 1797288555050958848 |
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| author | Ning-Ping Wang James Erskine Wei-Wei Zhang Rong-Hua Zheng Li-Hui Zhang Garret Duron Julian Gendreau Zhi-Qing Zhao |
| author_facet | Ning-Ping Wang James Erskine Wei-Wei Zhang Rong-Hua Zheng Li-Hui Zhang Garret Duron Julian Gendreau Zhi-Qing Zhao |
| author_sort | Ning-Ping Wang |
| collection | DOAJ |
| description | Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension. |
| first_indexed | 2024-03-07T18:51:12Z |
| format | Article |
| id | doaj.art-44bf585fc93440bb8d445f0b36060a85 |
| institution | Directory Open Access Journal |
| issn | 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T18:51:12Z |
| publishDate | 2017-05-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-44bf585fc93440bb8d445f0b36060a852024-03-02T01:21:46ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1752-89762017-05-011810.1177/147032031770665310.1177_1470320317706653Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin IINing-Ping Wang0James Erskine1Wei-Wei Zhang2Rong-Hua Zheng3Li-Hui Zhang4Garret Duron5Julian Gendreau6Zhi-Qing Zhao7Cardiovascular Research Laboratory, Mercer University School of Medicine, USADepartment of Internal Medicine, Navicent Health, USADepartment of Physiology, Shanxi Medical University, ChinaDepartment of Physiology, Shanxi Medical University, ChinaCardiovascular Research Laboratory, Mercer University School of Medicine, USACardiovascular Research Laboratory, Mercer University School of Medicine, USACardiovascular Research Laboratory, Mercer University School of Medicine, USADepartment of Physiology, Shanxi Medical University, ChinaIntroduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.https://doi.org/10.1177/1470320317706653 |
| spellingShingle | Ning-Ping Wang James Erskine Wei-Wei Zhang Rong-Hua Zheng Li-Hui Zhang Garret Duron Julian Gendreau Zhi-Qing Zhao Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II Journal of the Renin-Angiotensin-Aldosterone System |
| title | Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II |
| title_full | Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II |
| title_fullStr | Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II |
| title_full_unstemmed | Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II |
| title_short | Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II |
| title_sort | recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin ii |
| url | https://doi.org/10.1177/1470320317706653 |
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