Abstract 523: Autoantibodies To Heat Shock Protein 60 (hsp60) Promote Thrombus Formation In A Murine Model Of Arterial Thrombosis
Autoantibodies to heat shock protein (HSP) 60 are commonly produced following infection with HSP65-expressing microorganisms. These autoantibodies are associated with atherosclerosis and are known to affect endothelial cells in vitro. We hypothesized that anti-HSP60 autoantibodies could potentiate thrombosis, and evaluated the effect of antimurine HSP60 antibodies in a FeCl3-induced murine model of carotid artery injury. Anti-HSP60, or control, IgG was administered to BALB/c mice 48 h prior to inducing carotid artery injury, and blood flow was monitored using an ultrasound probe. Thrombus formation was more rapid and stable in anti-HSP60-treated mice, compared to controls (blood flow = 1.7±0.6% versus 34±12.6%, p=0.0157). Occlusion was complete in all anti-HSP60-treated mice (13/13), with no reperfusion observed. In contrast, 64% (9/14) of control mice had complete occlusion, with reperfusion occurring in 6/9 mice. Thrombi were significantly larger in anti-HSP60-treated mice (p=0.0001) and contained four-fold more inflammatory cells (p=0.0281) compared to controls. Non-injured contralateral arteries of anti-HSP60-treated mice were also affected, exhibiting abnormal endothelial cell morphology and significantly greater von Willebrand factor (vWf) expression than control mice (p=0.0024). In summary, anti-HSP60 autoantibodies altered endothelial cell morphology and vWf expression, and promoted arterial thrombosis and inflammatory cell recruitment. These findings suggest that anti-HSP60 autoantibodies may constitute an important prothrombotic risk factor in human vascular disease.