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Uhlorn, Josh; Husband, Nathaniel A.; Romero‐Aleshire, Melissa J.; Pollow, Dennis P.; Uhrlaub, Jennifer L.; Nikolich‐Zugich, Janko; Brooks, Heddwen L.
The FASEB journal, April 2018, 2018-04-00, Letnik: 32, Številka: S1Journal Article
There is extensive evidence that the immune system is required for the development of angiotensin II (Ang II) induced hypertension in males. In contrast, before entering menopause, we have shown that females are protected from T cell‐mediated Ang II hypertension. Following menopause, female protection from T cell‐mediated Ang II hypertension is lost; in the absence of T cells, systolic blood pressure (SBP) responses to Ang II in Rag‐1−/− postmenopausal mice were similar to those seen in premenopausal mice (SBP Δ12 ± 2 mmHg). After adoptive transfer of CD3+ T cells, Ang II significantly increased SBP in postmenopausal females (SBP Δ28 ± 3 mmHg; p<0.05). Thus, we hypothesize that the loss of estrogen in postmenopausal mice eliminates female protection to T cell‐mediated hypertension. Further, we examined if premenopausal protection from T cell‐mediated hypertension was due to T cell‐specific estrogen receptor alpha (ERα) signaling. CD3+ T cells were purified from ERα null mice (ERαKO) and adoptively transferred into cycling, female Rag‐1−/− mice (no T/B cells). Ang II was infused via osmotic mini‐pump for 14 days (490 ng/kg/min). Similar to our previous studies, cycling female Rag‐1−/− mice were resistant to T cell‐mediated Ang II hypertension following T cell transfer from wild type mice (SBP CD3+WT/Ang Δ6 ± 5 mmHg). Additionally, there was no significant difference in SBP when ERαKO T cells were adoptively transferred (SBP CD3+ ERαKO/Ang Δ5 ± 4 mmHg). Flow cytometric analysis of renal CD4+, CD8+, and regulatory Foxp3+ T cells identified that in the absence of ERα, there was an increase in expression of costimulatory receptor CD28 in all three T cell subsets (CD3+ ERαKO/Ang vs. CD3+WT/Ang: CD4+ 138%, CD8+ 144%, Foxp3+ 141%; p<0.05). Our studies suggest that loss of estrogen (menopause) increases female susceptibility to T cell‐mediated hypertension. However, loss of T cell‐specific ERα signaling does not seem to play a key role in premenopausal protection from T cell‐mediated Ang II hypertension. Support or Funding Information 1. T32HL007249 2. R01HL131834 This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
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