Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis

摘要: Atherosclerosis is a chronic inflammatory disorder of the arterial wall leading to coronary artery disease, stroke, and peripheral disease. Along with discovery dipeptidyl peptidase 4 (DPP4) as therapeutic target in type 2 diabetes, role for DPP4 atherosclerosis emerging. However, until now expression other DPPs such DPP8 DPP9 completely unknown. In present study, we first investigated DPP human atherosclerotic plaques. could only be observed endothelial cells plaque neovessels half specimens. contrast, were abundantly macrophage-rich regions We then focused on function macrophage differentiation, activation apoptosis. DPP8/9 was responsible most activity macrophages. During monocyte upregulated both pro-inflammatory M1 (3.7 ± 0.3-fold increase) anti-inflammatory M2 macrophages (3.7 ± 0.4-fold whereas remained unchanged. Inhibition compound 1G244 reduced (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 6.6 ± 1.9 ng/ml treated untreated cells), but not Likewise, silencing IL-6 secretion, pointing DPP9-mediated effect inhibitor. inhibition also enhanced apoptosis (15 ± 4 7 ± 3 % cells). Because play key atherogenesis, rupture subsequent infarction, might provide interesting prospects reducing and/or prevention rupture.