Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice
Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypo...
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| Format: | Article |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.588358/full |
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| author | Camila Manrique-Acevedo Camila Manrique-Acevedo Camila Manrique-Acevedo Jaume Padilla Jaume Padilla Huma Naz Huma Naz Makenzie L. Woodford Makenzie L. Woodford Thaysa Ghiarone Annayya R. Aroor Annayya R. Aroor Jack L. Hulse Francisco J. Cabral-Amador Vanesa Martinez-Diaz Chetan P. Hans Chetan P. Hans Adam Whaley-Connell Adam Whaley-Connell Adam Whaley-Connell Luis A. Martinez-Lemus Luis A. Martinez-Lemus Luis A. Martinez-Lemus Guido Lastra Guido Lastra |
| author_facet | Camila Manrique-Acevedo Camila Manrique-Acevedo Camila Manrique-Acevedo Jaume Padilla Jaume Padilla Huma Naz Huma Naz Makenzie L. Woodford Makenzie L. Woodford Thaysa Ghiarone Annayya R. Aroor Annayya R. Aroor Jack L. Hulse Francisco J. Cabral-Amador Vanesa Martinez-Diaz Chetan P. Hans Chetan P. Hans Adam Whaley-Connell Adam Whaley-Connell Adam Whaley-Connell Luis A. Martinez-Lemus Luis A. Martinez-Lemus Luis A. Martinez-Lemus Guido Lastra Guido Lastra |
| author_sort | Camila Manrique-Acevedo |
| collection | DOAJ |
| description | Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes. |
| first_indexed | 2024-12-19T12:58:11Z |
| format | Article |
| id | doaj.art-68eda70340d34485a839842d3f9aa89c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T12:58:11Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-68eda70340d34485a839842d3f9aa89c2022-12-21T20:20:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-03-011210.3389/fphys.2021.588358588358Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female MiceCamila Manrique-Acevedo0Camila Manrique-Acevedo1Camila Manrique-Acevedo2Jaume Padilla3Jaume Padilla4Huma Naz5Huma Naz6Makenzie L. Woodford7Makenzie L. Woodford8Thaysa Ghiarone9Annayya R. Aroor10Annayya R. Aroor11Jack L. Hulse12Francisco J. Cabral-Amador13Vanesa Martinez-Diaz14Chetan P. Hans15Chetan P. Hans16Adam Whaley-Connell17Adam Whaley-Connell18Adam Whaley-Connell19Luis A. Martinez-Lemus20Luis A. Martinez-Lemus21Luis A. Martinez-Lemus22Guido Lastra23Guido Lastra24Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesResearch Service, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United StatesDivision of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesResearch Service, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDivision of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDivision of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDivision of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDivision of Cardiovascular Medicine, Department of Medicine, University of Missouri, Columbia, MO, United StatesDivision of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesResearch Service, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, United StatesDivision of Nephrology and Hypertension, Department of Medicine, University of Missouri, Columbia, MO, United StatesDalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United StatesDepartment of Biomedical, Biological and Chemical Engineering, University of Missouri, Columbia, MO, United StatesDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, United StatesDivision of Endocrinology and Metabolism, Department of Medicine, University of Missouri, Columbia, MO, United StatesResearch Service, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, United StatesEnhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.https://www.frontiersin.org/articles/10.3389/fphys.2021.588358/fullarterial stiffeningmacrophageendotheliuminflammationadipose tissue |
| spellingShingle | Camila Manrique-Acevedo Camila Manrique-Acevedo Camila Manrique-Acevedo Jaume Padilla Jaume Padilla Huma Naz Huma Naz Makenzie L. Woodford Makenzie L. Woodford Thaysa Ghiarone Annayya R. Aroor Annayya R. Aroor Jack L. Hulse Francisco J. Cabral-Amador Vanesa Martinez-Diaz Chetan P. Hans Chetan P. Hans Adam Whaley-Connell Adam Whaley-Connell Adam Whaley-Connell Luis A. Martinez-Lemus Luis A. Martinez-Lemus Luis A. Martinez-Lemus Guido Lastra Guido Lastra Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice Frontiers in Physiology arterial stiffening macrophage endothelium inflammation adipose tissue |
| title | Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice |
| title_full | Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice |
| title_fullStr | Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice |
| title_full_unstemmed | Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice |
| title_short | Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice |
| title_sort | mineralocorticoid receptor in myeloid cells mediates angiotensin ii induced vascular dysfunction in female mice |
| topic | arterial stiffening macrophage endothelium inflammation adipose tissue |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.588358/full |
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