Abstract 19043: Rantes Dependent T Cell Recruitment into Perivascular Adipose Tissue n Angiotensin II Dependent Hypertension - Implications for Vascular Dysfunction and Blood Pressure Regulation
Hypertension (HT) is associated with T cell activation and their recruitment into perivascular adipose tissue (PVAT). We hypothesized that RANTES chemokine is critical for T cell recruitment into PVAT and therefore plays a role in hypertension and vascular dysfunction. Thus, we cytometrically analysed numbers and phenotype of T cells infiltrating perivascular adipose tissue in C57Bl6/J and RANTES -/- mice infused for 14 days with (angiotensin II (490mg/kg/d).
Results: AngII infusion caused increased PVAT leukocyte (CD45+) infiltration (2407±108 vs 654±70 cells/mg; p<0.01). This increase was particularly evident for CD3+ T cells (730±38 vs 140±23 cells/mg; p<0.01). Infiltration of CD4+ was higher than that of CD8+ (337±11 vs 229±11 cells/mg), but an infiltration with CD3+CD4-CD8- T cells (DN; constituting only 3-5% in blood) was particularly pronounced in pvAT (98±14 vs 23±3 cells/mg; p<0.05). Expression of RANTES chemokine receptor CCR5 on PVAT T cells was increased in HT (24±09% vs 17±08%; p<0.01) with highest prevalence on DN T cells and lowest on CD8+ (31±0.8% and 17±1.4%, respectively). RANTES-/- mice showed significantly decreased T cell infiltration of PVAT (394±80 vs 730±38, p<0.05) which was observed in all T cell subsets suggesting that RANTES is essential for vascular T cell homing. In particular reduced content of CCR5 in T cells infiltrating perivascular adipose tissue was observed (18±1.3% vs 24±09%; p<0.01). This was associated with protection of RANTES -/- from endothelial dysfunction measured as acetylocholine-induced NO dependent relaxations (p<0.05 by repeated measures ANOVA). In spite of that, RANTES -/- mice still developed severe hypertension (14 day:171±8.6 mmHg vs 154±3.9 in C57Bl6/J). Importantly, we observed that angiotensin II infusion caused increased PVAT infiltration with IL-17+CD4+ cells (1.3±0.3% vs 0.2±0.2%; p<0.05). This was further exacerbated in RANTES -/- mice (1.7±05% vs 1.3±0.3%).
Conclusions: In hypertension, RANTES is crucial for vascular T cell homing and is a major regulator of perivascular inflammation and endothelial dysfunction. Persistent augmented presence of Th17 cells may be associated with increased blood pressure in RANTES-/-, after Ang II administration.
- © 2012 by American Heart Association, Inc.