Role of the ubiquitin-proteasome system in carotid plaque instability in diabetic patients

Abstract

In order to define the role of the ubiquitin-proteasome system in atherosclerotic plaque rupture in patients with type 2 diabetes mellitus (T2DM), we evaluated the amount of this system, of the main inflammatory cells, of the collagen content and some indexes indicative of oxidative stress in the carotid plaques of both diabetic and non-diabetic asymptomatic patients. Plaques were obtained from 31 type 2 diabetic and 27 non-diabetic patients undergoing endoterectomy. Both were examined for macrophages, T-lymphocytes, ubiquitin/proteasome 20S activity, NFkB, IkB-b, nitrotyrosine, matrix metalloproteinase-9 (MMP-9) and collagen. Diabetic plaques had more macrophages,T-lymphocytes, inflammatory cells (HLA-DR), ubiquitin/proteasome, NFkB, nitrotyrosine, MMP-9 and lower collagen content and IkB-b levels, in comparison with non-diabetic plaques. These findings indicate that in diabetic patients, ubiquitin/proteasome overactivity is associated with enhanced inflammatory activity induced by diabetic oxidative stress. This induces the NFkB release into the nucleus which, in turn, is responsible for the expression of inflammatory cytokines causing plaque rupture.