Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects

• Published in: Cardiovascular diabetology Vol. 16; no. 1; pp. 99 - 9
• Main Authors: Giovannini, Silvia, Tinelli, Giovanni, Biscetti, Federico, Straface, Giuseppe, Angelini, Flavia, Pitocco, Dario, Mucci, Luciana, Landolfi, Raffaele, Flex, Andrea
• Format: Journal Article
• Language: English
• Published: England BioMed Central 08.08.2017; BMC
• Subjects: Aged; Atherosclerosis; Biomarkers - blood; Blood pressure; C-reactive protein; C-Reactive Protein - analysis; Calcification; Calcification (ectopic); Cardiovascular disease; Cardiovascular diseases; Cell adhesion & migration; Coronary vessels; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Female; Gene expression; High mobility group proteins; HMGB-1; HMGB1 Protein - blood; Humans; Hypertension; Inflammation; Interleukin 6; Ischemia; Male; Middle Aged; Mobility; OPG; Original Investigation; Osteoporosis; Osteoprotegerin; Osteoprotegerin - blood; PAD; Peripheral Arterial Disease - blood; Peripheral Arterial Disease - complications; Proteins; Retrospective Studies; Risk Factors; Serum levels; Studies; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Type 2 diabetes; Vascular Calcification - complications; Type 2 diabetes; PAD; OPG; HMGB-1
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-017-0581-z

High mobility group box-1 (HMGB-1) is a nuclear protein also acting as inflammatory mediator, whilst osteoprotegerin (OPG), member of tumor necrosis factor receptor superfamily, is indicated as marker of vascular calcification. Peripheral artery disease (PAD) and type 2 diabetes (T2D) are clinical conditions characterized by elevated serum inflammatory markers and vascular calcification enhancement. The aim of this study was to investigate the potential role of HMGB-1, OPG and several inflammatory mediators such as C-reactive protein (HsCRP), tumor necrosis factor-alpha and interleukin-6 (IL-6) on the presence and severity of peripheral artery disease in patients with T2D. In this retrospective observational study, we have analyzed HMGB-1, OPG and inflammatory cytokines serum levels in 1393 type 2 diabetic patients with PAD and without PAD (WPAD). HMGB-1 (7.89 ± 15.23 ng/mL), OPG (6.54 ± 7.76 pmol/L), HsCRP (15.6 ± 14.4 mg/L) and IL-6 (56.1 ± 28.6 pg/mL) serum levels were significantly higher in patients with PAD than in those WPAD (3.02 ± 8.12 ng/mL, P ˂ 0.001; 2.98 ± 2.01 pmol/L, P < 0.001; 7.05 ± 4.4 mg/L, P < 0.001; 37.5 ± 20.2 pg/mL, P < 0.001 respectively). Moreover HMGB-1 (P < 0.001), OPG (P < 0.001), HsCRP (P < 0.001) and IL-6 (P < 0.001) serum levels were positively correlated with clinical severity of PAD. HMGB-1 (adjusted OR 12.32; 95% CI 3.56-23.54, P = 0.023) and OPG (adjusted OR 3.53; 95% CI 1.54-6.15, P = 0.019) resulted independent determinants of PAD in patients with T2D after adjusting for the conventional cardiovascular risk factor and established inflammatory mediators. In T2D patients HMGB-1 and OPG serum levels are higher in patients affected by PAD and independently associated with its occurrence and clinical severity.