Abstract 15819: Immune Regulatory T Cells Improve Vascular Function Through the Inhibition of Autophagy in Established Hypertension
Introduction: Growing studies report the involvement of immune T regulatory cells (Treg) in vascular complications in hypertension. We recently demonstrated that transfer of Treg cells before the development of hypertension prevents the development of hypertension and impaired vascular endothelium-dependent relaxation (EDR) in mice infused with angiotensin II (Ang II).
Hypothesis: In this study, we determined whether we could rescue vascular function in an animal model with established hypertension by one single injection of Treg cells and whether Treg cells improve vascular function through the inhibition of autophagy and oxidative stress.
Methods: Hypertension (HT) was induced by angiotensin II (Ang II, 400 ng/kg/min) for 4 weeks. Treg cells were isolated from control mice and then injected as a single bolus at the end of the second week for 2 weeks in the presence of Ang II. In another group, mice were injected daily with chloroquine (autophagy inhibitor, 10 mg/Kg) starting at the end of the second week for 2 weeks in the presence of Ang II. Blood pressure was measured once a week. At the end of experiment, EDR in mesenteric resistance artery (MRA) was assessed using wire myography, autophagy markers (Atg7, Atg5 and Beclin-1) were determined with Western blot analysis, and oxidative stress was assessed with NADPH oxidase activity.
Results: The EDR was significantly reduced associated with an increase in autophagy markers (Atg7, Atg5 and Beclin-1), and oxidative stress in MRA from HT compared to control mice. The one single transfer of Treg cells to the hypertensive mice did not change the blood pressure but significantly improved the EDR through the inhibition of the autophagy markers and oxidative stress. The daily inhibition of autophagy reduced blood pressure, improved the EDR, and markedly decreased the autophagy markers as well as the oxidative stress.
Conclusions: Our data demonstrate that one single injection of Treg cells can rescue the EDR in a mouse with established hypertension through the inhibition of autophagy and oxidative stress-dependent mechanism.
Author Disclosures: E. Radwan: None. V. Mali: None. M. Trebak: None. K. Matrougui: None.
- © 2016 by American Heart Association, Inc.