Abstract 16: Adoptive Transfer of T Lymphocytes Prevents Angiotensin II-induced Vascular Stiffness in rag-1 Knockout Mice.
Background: Both innate and adoptive immune systems are involved in the pathogenesis of hypertension and vascular damage. T lymphocytes participate in the low-grade inflammatory response that contributes to vascular injury in cardiovascular disease, including hypertension. Angiotensin (Ang) II-induced hypertension and endothelial dysfunction are blunted in rag1 knockout (rag1-/-) mice, which are deficient in T and B lymphocytes, and restored with adoptive transfer of T but not B lymphocytes. We hypothesized that adoptive transfer of T lymphocytes from C57Bl/6 mice (WT) will exacerbate Ang II-induced vascular damage in rag1-/- mice.
METHODS: Eleven-week old male rag1-/- mice were injected i.v. with PBS or 10 x 106 pan T lymphocytes, and 2 weeks later implanted with a dummy pump (control) or infused with Ang II (490 ng/kg/min, s.c.) for 14 days (n=5-8). Systolic (SBP) and diastolic blood pressure (SBP) were measured by telemetry. Endothelial function and vessel structure were assessed in second order mesenteric arteries by pressurized myography. Successful adoptive transfer was confirmed at time of sacrifice by determining numbers of T cells in the spleen by flow cytometry.
Results: Ang II induced a similar 40 mmHg SBP rise in rag-1-/- mice injected with PBS or T cells, but DBP rise was greater for T cell-injected mice (24 mmHg) than for PBS injected mice (9 mmHg). Ang II impaired vasodilatory responses to acetylcholine in T cell-injected mice (54.0±5.9%) but not in PBS injected mice (82.1±2.9%). Ang II treatment induced hypertrophic remodeling in PBS injected mice, but not in T cell-injected mice (media-to-lumen ratio: 4.1±0.3 from 2.7±0.3 vs. 3.3±0.2 from 2.6±0.1, media cross-sectional area (μm2): 5757±565 from 4382±580 vs. 4811±281 from 4350±254). Ang II increased vascular stiffness, indicated by a leftward shift of the small artery stress/strain relationship, in PBS injected mice but to a lower extent in T cell-injected mice.
Conclusions: These findings suggest that T lymphocytes have a protective role in Ang II-induced vascular stiffness.
- © 2012 by American Heart Association, Inc.