Abstract
Introduction:
T lymphocytes participate in the low-grade inflammatory response that causes vascular injury in angiotensin (Ang) II-induced hypertension. Ang II-induced hypertension and endothelial dysfunction are blunted in T and B lymphocyte-deficient (
Rag1
-/-
) mice, and restored with reconstitution of T cells. However, the role of T regulatory lymphocytes (Treg) in Ang II-induced vascular injury is unclear. We hypothesized that adoptive transfer of FOXP3-deficient (Scurfy) T lymphocytes vs. wild-type (WT) cells will exacerbate Ang II-induced vascular damage in
Rag1
-/-
mice.
Methods:
Eleven-week old male
Rag1
-/-
mice were injected IV with PBS/2% FBS (control), 10
7
WT or Scurfy T lymphocytes, and 2 weeks later underwent sham surgery or were infused with Ang II (490 ng/kg/min, s.c.) using mini-osmotic pumps for 14 days (n=3-8). Systolic (SBP) and diastolic (DBP) blood pressure were measured by telemetry. Vascular function and structure were assessed in second order mesenteric arteries by pressurized myography. Reactive oxygen species (ROS) production and fibronectin and collagen I and III expression were determined in aorta.
Results:
Ang II induced a 40 mmHg SBP rise in
Rag1
-/-
mice for all treatment groups, but DBP rise was ~10 mmHg greater for WT and Scurfy T cell-injected mice than for control mice (
P
<0.01). Adoptive transfer of WT T cells restored Ang II induced-endothelial dysfunction in mesenteric arteries (
P
<0.05), which was exaggerated in Scurfy T cell-injected mice (
P
<0.01). Ang II induced a greater increase in ROS production in aortic perivascular fat of Scurfy T cell-injected mice compared to WT T cell-injected mice (
P
<0.05). Ang II induced mesenteric artery stiffness (
P
<0.01) and hypertrophic remodeling (
P
<0.05) in control and Scurfy T cell-injected mice, but not in WT T cell-injected mice. Ang II increased fibronectin expression to a greater extent in the aorta of control and Scurfy T cell-injected mice compared to WT T cell-injected mice (
P
<0.01). Collagen I and III content was greater in the aorta of control and Scurfy T cell-injected mice than in WT T cell-injected mice (
P
<0.01), but expression was unaltered by Ang II treatment.
Conclusion:
Foxp3+ T regulatory lymphocytes have a protective role against Ang II-induced vascular remodeling.