Abstract 14: T Cells Mediate Angiotensin II-induced Aortic Stiffening

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Clinical studies show an association between inflammation and arterial stiffness. We and others have shown that T cells are involved in hypertension; however their role in aortic stiffening is unknown. We hypothesized that T cells mediate angiotensin II-induced aortic stiffening. Using a pressurized myograph system, we determined aortic stiffness and quantified this using a distensibility index (DI), defined as the percent change in aortic outer diameter from 75 mmHg to 125 mmHg. Angiotensin II (490ng/kg/min for 14 days) markedly decreased the distensibility index in C57Bl/6 mice (23.8±5.5 v.s. 8.9±4.1, p<0.01, n=8), and this was almost completely prevented in RAG-1 -/- mice (18.3±4.0, p<0.01 compared with C57Bl/6, n=8). Adoptive transfer of pan T cells into RAG-1 -/- mice restored aortic stiffness in RAG-1 -/- (11.9±2.6, p<0.05, n=5). The effect of T cell-derived pro-inflammatory cytokines on aortic stiffening was examined using interferon-γ (IFN-γ -/- ) and IL-6 -/- mice. Deficiency of INF-γ partially restored aortic distensibility (17.0±3.5 v.s. 8.9±4.1, p<0.01, n=8) compared C57Bl/6 mice treated with angiotensin II. Aortic distensibility was also preserved in IL-6 -/- mice (19.9±5.9 v.s. 8.9±4.1, p<0.01, n=8) treated with angiotensin II. In contrast to these functional alterations, the increase in collagen caused by angiotensin II was similar between wild-type and RAG-1 -/- mice. There was no change in elastin abundance with angiotensin II treatment or in different mouse strains. In conclusion, T cells are essential for angiotensin II-induced collagen deposition, vascular hypertrophy and aortic stiffening. Part of these effects could be mediated by pro-inflammatory cytokines such as INF-γ and IL-6. These likely mediate aortic stiffening by altering properties of elastin and collagen such as crosslinking, rather than alter total abundance of these proteins.