T‐cell dependent IL‐6 signaling mediates angiotensin II‐enhanced microvascular thrombosis

Hypertension is associated with a prothrombotic and hypercoagulable state. Angiotensin II (AngII) is a key mediator of the thrombotic abnormalities that accompany hypertension. However, the mechanisms that underlie the prothrombotic actions of AngII remain poorly understood. We have previously demonstrated that AngII enhances thrombus development in the microvasculature and that T‐lymphocytes contribute to the AngII‐enhanced microvascular thrombosis. We have examined the role of interleukin‐6 (IL‐6) in the AngII‐enhanced thrombosis response and assessed whether/how the actions of IL‐6 are linked to T‐cells. Thrombus formation in cremaster arterioles was induced using the light/dye endothelial cell injury model. Wild type (WT) mice, IL‐6 −/− mice, and immunodeficient Rag‐1 −/− injected with T cells from WT or IL‐6 −/− mice were infused (14 d) with AngII (1 μg/kg/min). Some AngII infused WT mice were treated (24 hrs before the thrombus formation) with a blocking antibody directed against either the alpha or beta (gp130) chain of the IL‐6 receptor (IL‐6r). We found that IL‐6 −/− mice, Rag‐1 −/− mice reconstituted with IL‐6 −/− (but not WT) T cells, and WT mice treated with either IL‐6r antibody were significantly protected against the prothrombotic actions of chronic AngII administration. These findings link IL‐6 signaling to the T‐cell dependent prothrombotic effects of AngII. (Supported by HL26441)