Abstract: TH-OR27
Role of Human T Cells in Hypertension and Hypertensive Organ Damage
Session Information
- Hypertension and CVD: Epidemiology, Risk Factors, Prevention
November 03, 2022 | Location: W240, Orange County Convention Center‚ West Building
Abstract Time: 05:15 PM - 05:24 PM
Category: Hypertension and CVD
- 1503 Hypertension and CVD: Mechanisms
Authors
- Rahman, Masudur, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
- Stegbauer, Johannes, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
- Yakoub, Mina, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
- Arifaj, Denada, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
- Hering, Lydia, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
- Rump, Lars C., Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Nordrhein-Westfalen, Germany
Background
Inflammation seems to influence hypertension and hypertensive organ damage. Animal studies suggest that adaptive immunity, in particular T cells contribute to the development hypertension. Due to the complex pathophysiological interactions in vivo, the impact of human T cells in the development of hypertension and hypertensive organ damage is still unknown.
Methods
To investigate the impact of human T cells in hypertension, we transferred T cells from treatment resistant hypertensive patients (TRH) and healthy controls (controls) into immunodeficient NOD.Cg-Prkdcscid H2-K1tm1Bpe H2-D1tm1Bpe Il2rgtm1Wjl/SzJ (NSG-(KbDb)null) mice to establish a humanized mouse model. Hypertension was induced by angiotensin (Ang)II (500ng/kg/min) infusion for 14 days.
Results
PBMCs from RHT or controls were transferred to NSG-(KbDb) null mice. After ensuring T cell engraftment, blood pressure (BP) was measured by radiotelemetry. At baseline, systolic BP did not differ, however, systolic BP in response to AngII was increased in NSG-(KbDb) null mice receiving PBMCs from TRH compared to controls (week 1: 133±6 vs. 162±3mmHg, p<0.01; week 2: 141±6 vs. 158±7mmHg, n=5-6, p<0.05). Moreover, endothelial-dependant vasorelaxation was significantly impaired in isolated perfused kidneys of NSG-(KbDb) null mice receiving PBMCs from TRH compared to controls. Proportions of effector memory CD4 and Th17 CD4 cells in the spleens and kidneys of NSG-(KbDb) null mice engrafted with PBMCs from TRH were significantly higher compare to controls. Furthermore, renal mRNA expression of TNFα derived from human T cells (p<0.05) and renal perivascular T cell infiltration were significantly higher in NSG-(KbDb) null mice engrafted with PBMCs from TRH compared to controls. Overnight incubation of aortic rings with human TNFα impaired endothelial-dependen vasorelaxation compared to untreated aortic rings (p<0.01). Finally, NSG-(KbDb) null mice engrafted with PBMC from TRH were treated with the TNFα inhibitor etanercept. TNFα inhibition attenuated the systolic BP response to AngII compared to untreated mice (132±1 vs. 160±2mmHg, n=6, p<0.01).
Conclusion
The present results suggest that pro-inflammatory cytokines released by T cells from patients with TRH directly influence the development of hypertension and therefore may have a pathophysiological relevance in the genesis of human hypertension.