Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice
Adhesion of monocytes to the vascular endothelium frequently leads to an inflammatory response, which contributes to hypertension and vascular remodeling. Vascular cellular adhesion molecule-1 (VCAM-1) plays an important role in leukocyte adhesion and migration during inflammatory diseases. However,...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.825459/full |
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| author | Liangqingqing Yin Jie Bai Wei-Jia Yu Ying Liu Hui-Hua Li Hui-Hua Li Qiu-Yue Lin |
| author_facet | Liangqingqing Yin Jie Bai Wei-Jia Yu Ying Liu Hui-Hua Li Hui-Hua Li Qiu-Yue Lin |
| author_sort | Liangqingqing Yin |
| collection | DOAJ |
| description | Adhesion of monocytes to the vascular endothelium frequently leads to an inflammatory response, which contributes to hypertension and vascular remodeling. Vascular cellular adhesion molecule-1 (VCAM-1) plays an important role in leukocyte adhesion and migration during inflammatory diseases. However, its role in angiotensin (Ang) II -induced hypertension and vascular dysfunction remains largely unknown. Wild-type (WT) mice were administered a VCAM-1 neutralizing antibody (0.1 or 0.2 mg/mouse/day) or IgG control and then infused with Ang II (490 ng kg−1 min−1) or saline continuously for 14 days. Systolic blood pressure (SBP) was measured with a tail-cuff system, pathological changes in the aorta were assessed by histological staining, and vascular relaxation was analyzed an aortic ring assay. Our results indicated that compared with saline infusion, Ang II infusion significantly upregulated VCAM-1 expression in the mouse aorta and serum. Moreover, Ang II infusion markedly increased arterial hypertension, wall thickness, fibrosis, infiltration of Mac-2+ macrophages, reactive oxygen species (ROS) production and vascular relaxation dysfunction. Conversely, blockade of VCAM-1 with a neutralizing antibody substantially alleviated these effects. In vitro experiments further confirmed that the VCAM-1 neutralizing antibody inhibited Ang II-induced macrophage adhesion and migration and DNA damage and oxidative stress in endothelial cells (ECs). In conclusion, these results indicate that blockade of VCAM-1 exerts a protective effect against Ang II-induced arterial hypertension and dysfunction by regulating monocytes adhesion and infiltration into the endothelium and represents a novel therapeutic approach for hypertension. |
| first_indexed | 2024-12-13T13:25:14Z |
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| id | doaj.art-8b555b54c8ac45439dc6938ff70e78da |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T13:25:14Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-8b555b54c8ac45439dc6938ff70e78da2022-12-21T23:44:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-02-011310.3389/fphar.2022.825459825459Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in MiceLiangqingqing Yin0Jie Bai1Wei-Jia Yu2Ying Liu3Hui-Hua Li4Hui-Hua Li5Qiu-Yue Lin6Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Emergency Medicine, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaAdhesion of monocytes to the vascular endothelium frequently leads to an inflammatory response, which contributes to hypertension and vascular remodeling. Vascular cellular adhesion molecule-1 (VCAM-1) plays an important role in leukocyte adhesion and migration during inflammatory diseases. However, its role in angiotensin (Ang) II -induced hypertension and vascular dysfunction remains largely unknown. Wild-type (WT) mice were administered a VCAM-1 neutralizing antibody (0.1 or 0.2 mg/mouse/day) or IgG control and then infused with Ang II (490 ng kg−1 min−1) or saline continuously for 14 days. Systolic blood pressure (SBP) was measured with a tail-cuff system, pathological changes in the aorta were assessed by histological staining, and vascular relaxation was analyzed an aortic ring assay. Our results indicated that compared with saline infusion, Ang II infusion significantly upregulated VCAM-1 expression in the mouse aorta and serum. Moreover, Ang II infusion markedly increased arterial hypertension, wall thickness, fibrosis, infiltration of Mac-2+ macrophages, reactive oxygen species (ROS) production and vascular relaxation dysfunction. Conversely, blockade of VCAM-1 with a neutralizing antibody substantially alleviated these effects. In vitro experiments further confirmed that the VCAM-1 neutralizing antibody inhibited Ang II-induced macrophage adhesion and migration and DNA damage and oxidative stress in endothelial cells (ECs). In conclusion, these results indicate that blockade of VCAM-1 exerts a protective effect against Ang II-induced arterial hypertension and dysfunction by regulating monocytes adhesion and infiltration into the endothelium and represents a novel therapeutic approach for hypertension.https://www.frontiersin.org/articles/10.3389/fphar.2022.825459/fullVCAM-1hypertensionmacrophage adhesioninflammationoxidative stressvascular dysfunction |
| spellingShingle | Liangqingqing Yin Jie Bai Wei-Jia Yu Ying Liu Hui-Hua Li Hui-Hua Li Qiu-Yue Lin Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice Frontiers in Pharmacology VCAM-1 hypertension macrophage adhesion inflammation oxidative stress vascular dysfunction |
| title | Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice |
| title_full | Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice |
| title_fullStr | Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice |
| title_full_unstemmed | Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice |
| title_short | Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice |
| title_sort | blocking vcam 1 prevents angiotensin ii induced hypertension and vascular remodeling in mice |
| topic | VCAM-1 hypertension macrophage adhesion inflammation oxidative stress vascular dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.825459/full |
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