Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population

Cardiovascular Diabetology

Giuseppe Straface¹  Vincenzo Arena²  Maria Margherita Rando³  Federico Biscetti⁴  Andrea Flex⁵  Massimo Massetti⁶  Antonio Gasbarrini⁷  Dario Pitocco⁸  Giovanni Tinelli⁹  Andrea Leonardo Cecchini^1,10  Elisabetta Nardella^1,10  Flavia Angelini^1,10  Marco Filipponi^1,11 

[1] Department of Internal Medicine, St. M. Goretti Hospital, Roma, Italy;Department of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Cardiovascular Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University School of Medicine, Largo Francesco Vito, 1, 00168, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Cardiovascular Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University School of Medicine, Largo Francesco Vito, 1, 00168, Roma, Italy;Laboratory of Vascular Biology and Genetics, Università Cattolica del Sacro Cuore, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Cardiovascular Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University School of Medicine, Largo Francesco Vito, 1, 00168, Roma, Italy;Laboratory of Vascular Biology and Genetics, Università Cattolica del Sacro Cuore, Roma, Italy;Università Cattolica del Sacro Cuore, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Università Cattolica del Sacro Cuore, Roma, Italy;Cardiovascular Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Università Cattolica del Sacro Cuore, Roma, Italy;Department of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Università Cattolica del Sacro Cuore, Roma, Italy;Diabetology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Vascular Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy;Università Cattolica del Sacro Cuore, Roma, Italy;Laboratory of Vascular Biology and Genetics, Università Cattolica del Sacro Cuore, Roma, Italy;Ospedale San Giovanni Battista-ACISMOM, Roma, Italy;

关键词: Diabetes mellitus;    Internal carotid artery stenosis (ICAS);    High mobility group box-1 (HMGB1);   

DOI  :  10.1186/s12933-021-01304-8

来源: Springer

【 摘 要 】

BackgroundCarotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population.Research design and methodsWe studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions.ResultsWe found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients.ConclusionsThe present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

【 授权许可】

CC BY