Abstract
Abstract P137: Knock Out Of Regulatory G Protein Signaling 2 Specifically In CD4 T Cells Prevents Angiotensin II Induced Hypertension
Hypertension (Dallas, Tex. 1979), Vol.76(Suppl_1)
09/2020
DOI: 10.1161/hyp.76.suppl_1.P137
Abstract
Preeclampsia (PreE) is a hypertensive disorder in pregnancy. Aberrations of Regulator of G protein Signaling (RGS) family members are associated with PreE and hypertension (HTN). We previously observed a 9-fold increase in RGS2 in CD4+ T cells during PreE. In total, our work suggests that modulating T cells may be a therapeutic strategy for HTN. We hypothesize that reducing RGS2 specifically in CD4+ T cells will restore anti-inflammatory T cell responses and prevent HTN.
Utilizing an angiotensin (ANG) II infusion mouse model, we aimed to investigate 1) the impact of the loss of RGS2 in CD4+ T cells on cytokine production and 2) if the loss of RGS2 in CD4+ T cells will protect against the development of HTN. RGS2 was knocked-out in CD4+ T cells (CD4-Cre x RGS2
flox
mice;
KO
). CD4 RGS2
KO
(n=5) or littermate control mice (CTL, n=3) were administered 490 ng/kg/min ANG II for 21 days via mini-osmotic pump. Blood pressure was assessed by radiotelemetry. ELISAs were performed to determine pro- and anti- inflammatory cytokine levels in tissues from KO (n=9) and CTL (n=8) mice.
Pro-inflammatory cytokines IFNγ and IL-17 were not significantly different in the heart, kidney, liver or spleen of KO vs CTL mice. The anti-inflammatory cytokines IL-4 (KO 410 vs CTL 339 pg/mL, p<0.05) and TGFβ (KO 5.7x10
5
vs 5.0x10
5
pg/mL, p<0.05) were increased in the kidneys of KO mice compared to CTL mice. At baseline, KO and CTL mice showed no differences in 24-hr heart rate (HR), systolic or diastolic blood pressure (SBP and DBP, respectively). Throughout the study, KO mice had a significantly lower 24-hr SBP (Day 7: KO 132.3 vs CTL 149.7 mmHg, p<0.05; Day 14: KO 123.6 vs CTL 162.3 mmHg, p<0.05; Day 21: KO 118.3 vs 154.8 mmHg, p<0.05) and DBP (Day 7: KO 101.2 vs CTL 113.8 mmHg, p<0.05; Day 14: KO 98.4 vs CTL 121.8 mmHg, p<0.05; Day 21: KO 96.8 vs 116.4 mmHg, p<0.05) compared to CTL mice. The 24-hr HR was only significantly lower at three weeks ANG II (KO 493.4 vs CTL 540.6 bpm, p<0.05) compared to CTL mice.
The increased levels of IL-4 and TGFβ observed in KO mice support a role of RGS2 in anti-inflammatory immune responses. In accordance with our hypothesis, the loss of RGS2, specifically in CD4+ T cells prevented ANG II-induced hypertension. Therefore, RGS2 expression in CD4+ T cells plays a critical role in the development of HTN.
Details
- Title: Subtitle
- Abstract P137: Knock Out Of Regulatory G Protein Signaling 2 Specifically In CD4 T Cells Prevents Angiotensin II Induced Hypertension
- Creators
- Sabrina M Scroggins - University of IowaGabrielle Gray - University of IowaMonica C Myers - University of IowaSarah N Miller - University of IowaPablo Nakagawa - Medical College of WisconsinDonna A Santillan - University of IowaJustin L Grobe - Medical College of WisconsinMark K Santillan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.76(Suppl_1)
- DOI
- 10.1161/hyp.76.suppl_1.P137
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2020
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984316895002771
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