T Regulatory lymphocytes prevent angiotensin ii–induced hypertension and vascular injury

T Barhoumi, DA Kasal, MW Li, L Shbat, P Laurant… - …, 2011 - Am Heart Assoc
Hypertension, 2011Am Heart Assoc
Angiotensin (Ang) II induces hypertension by mechanisms mediated in part by adaptive
immunity and T effector lymphocytes. T regulatory lymphocytes (Tregs) suppress T effector
lymphocytes. We questioned whether Treg adoptive transfer would blunt Ang II–induced
hypertension and vascular injury. Ten-to 12-week–old male C57BL/6 mice were injected IV
with 3× 105 Treg (CD4+ CD25+) or T effector (CD4+ CD25−) cells, 3 times at 2-week
intervals, and then infused or not with Ang II (1 μg/kg per minute, SC) for 14 days. Ang II …
Angiotensin (Ang) II induces hypertension by mechanisms mediated in part by adaptive immunity and T effector lymphocytes. T regulatory lymphocytes (Tregs) suppress T effector lymphocytes. We questioned whether Treg adoptive transfer would blunt Ang II–induced hypertension and vascular injury. Ten- to 12-week–old male C57BL/6 mice were injected IV with 3×105 Treg (CD4+CD25+) or T effector (CD4+CD25) cells, 3 times at 2-week intervals, and then infused or not with Ang II (1 μg/kg per minute, SC) for 14 days. Ang II increased systolic blood pressure by 43 mm Hg (P<0.05), NADPH oxidase activity 1.5-fold in aorta and 1.8-fold in the heart (P<0.05), impaired acetylcholine vasodilatory responses by 70% compared with control (P<0.05), and increased vascular stiffness (P<0.001), mesenteric artery vascular cell adhesion molecule expression (2-fold; P<0.05), and aortic macrophage and T-cell infiltration (P<0.001). All of the above were prevented by Treg but not T effector adoptive transfer. Ang II caused a 43% decrease in Foxp3+ cells in the renal cortex, whereas Treg adoptive transfer increased Foxp3+ cells 2-fold compared with control. Thus, Tregs suppress Ang II–mediated vascular injury in part through anti-inflammatory actions. Immune mechanisms modulate Ang II–induced blood pressure elevation, vascular oxidative stress, inflammation, and endothelial dysfunction.
Am Heart Assoc