| Autor: |
Uhlorn JA; Department of Physiology College of Medicine University of Arizona Tucson AZ., Husband NA; Department of Physiology College of Medicine University of Arizona Tucson AZ., Romero-Aleshire MJ; Department of Physiology College of Medicine University of Arizona Tucson AZ., Moffett C; Department of Physiology College of Medicine University of Arizona Tucson AZ., Lindsey ML; Department of Cellular and Integrative Physiology Center for Heart and Vascular Research Nebraska-Western Iowa Health Care SystemUniversity of Nebraska Medical Center and Research Service Omaha NE., Langlais PR; Department of Medicine College of Medicine University of Arizona Tucson AZ., Brooks HL; Department of Physiology College of Medicine University of Arizona Tucson AZ. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Heart Association [J Am Heart Assoc] 2021 Jan 19; Vol. 10 (2), pp. e018038. Date of Electronic Publication: 2021 Jan 07. |
| DOI: |
10.1161/JAHA.120.018038 |
| Abstrakt: |
Background Menopause is associated with an increase in the prevalence and severity of hypertension in women. Although premenopausal females are protected against T cell-dependent immune activation and development of angiotensin II (Ang II) hypertension, this protection is lost in postmenopausal females. Therefore, the current study hypothesized that specific CD4 + T cell pathways are regulated by sex hormones and Ang II to mediate progression from premenopausal protection to postmenopausal hypertension. Methods and Results Menopause was induced in C57BL/6 mice via repeated 4-vinylcyclohexene diepoxide injections, while premenopausal females received sesame oil vehicle. A subset of premenopausal mice and all menopausal mice were infused with Ang II for 14 days (Control, Ang II, Meno/Ang II). Proteomic and phosphoproteomic profiles of CD4 + T cells isolated from spleens were examined. Ang II markedly increased CD4 + T cell protein abundance and phosphorylation associated with DNA and histone methylation in both premenopausal and postmenopausal females. Compared with premenopausal T cells, Ang II infusion in menopausal mice increased T cell phosphorylation of MP2K2, an upstream regulator of ERK, and was associated with upregulated phosphorylation at ERK targeted sites. Additionally, Ang II infusion in menopausal mice decreased T cell phosphorylation of TLN1, a key regulator of IL-2Rα and FOXP3 expression. Conclusions These findings identify novel, distinct T cell pathways that influence T cell-mediated inflammation during postmenopausal hypertension. |
| Databáze: |
MEDLINE |
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