Cd4+ T cell-specific proteomic pathways identified in progression of hypertension across postmenopausal transition
Author
Uhlorn, J.A.Husband, N.A.
Romero-Aleshire, M.J.
Moffett, C.
Lindsey, M.L.
Langlais, P.R.
Brooks, H.L.
Affiliation
Department of Physiology, College of Medicine, University of ArizonaDepartment of Medicine, College of Medicine, University of Arizona
Issue Date
2021
Metadata
Show full item recordPublisher
American Heart Association Inc.Citation
Uhlorn, J. A., Husband, N. A., Romero‐Aleshire, M. J., Moffett, C., Lindsey, M. L., Langlais, P. R., & Brooks, H. L. (2021). CD4+ T Cell‐Specific Proteomic Pathways Identified in Progression of Hypertension Across Postmenopausal Transition. Journal of the American Heart Association, 10(2), e018038.Rights
Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
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. © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.Note
Open access journalISSN
2047-9980Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1161/JAHA.120.018038
Scopus Count
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Except where otherwise noted, this item's license is described as Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License.

