T‐lymphocytes contribute to angiotensin II‐mediated thrombosis in cremaster muscle arterioles

While there is mounting evidence that chronic arterial hypertension is associated with altered hemostatic, inflammatory and immune systems, the nature of the interaction between these systems remain poorly understood. The aim of this study was to assess the contribution of T cells and cytokines (TNF‐α, IFN‐γ, IL‐6) to the arteriolar thrombosis induced by AngII infusion (2 wks, 1 ug/kg/min). Intravital microscopy was used to quantify the time to thrombus initiation and to flow cessation in murine cremaster muscle arterioles exposed to light/dye activation. AngII‐enhanced thrombus development was evaluated in the following experimental groups: WT mice, immunodeficient Rag‐1 −/− mice, Rag‐1 −/− reconstituted with T cells from WT donors, and in the following cytokine‐deficient mice: TNF‐α −/− , IFN‐γ −/− and IL‐6 −/− mice. While WT mice exhibited accelerated thrombosis in response to AngII infusion, this was not observed in Rag–1 −/− mice. Adoptive transfer of WT T cells into Rag‐1 −/− mice restored the AngII‐induced thrombus response. IFN‐γ −/− mice exhibited a thrombosis response similar to WT mice. The time to thrombus initiation was extended in TNF‐α −/− mice. However, AngII did not induce an acceleration of either phase of thrombus formation in IL‐6 −/− mice. Our study provides novel evidence implicating both T‐lymphocytes and IL‐6 in the accelerated thrombosis associated with AngII‐induced hypertension. (HL26441).