HMGB1 in vascular diseases: Its role in vascular inflammation and atherosclerosis

The nuclear protein high mobility group box 1 (HMGB1) has been suggested to be involved in the pathogenesis of several vascular diseases such as systemic vasculitis and atherosclerosis. In systemic vasculitides including ANCA-associated vasculitis and Kawasaki disease, serum HMGB1 levels are higher in patients with active disease compared to healthy controls. In atherosclerotic disease, HMGB1 displays increased expression in nuclei and cytoplasm of macrophages and smooth muscle cells in the atherosclerotic lesions, and is implicated in the progression of the atherosclerotic plaque. Experimental models of acute coronary syndromes and cerebrovascular accidents show that HMGB1 is not only involved in the amplification of the inflammatory response during acute ischemic injury, but also in the recovery and remodeling process after ischemia. Patients with acute coronary syndromes or stroke present significantly higher serum levels of HMGB1 than healthy controls and levels are associated with disease severity and mortality. Here we review clinical and experimental studies dealing with the role of HMGB1 in vascular diseases.