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.
Cardiovasc Diabetol. 2021 May 27;20(1):114. doi: 10.1186/s12933-021-01304-8.
Carotid 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.
We 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.
We 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.
The 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.
颈动脉粥样硬化是糖尿病的并发症之一。特别是斑块不稳定会导致疾病进展和中风的发生。高迁移率族蛋白 B1（HMGB1）是一种核蛋白，参与动脉粥样硬化和心血管疾病的发生和发展。本研究旨在分析糖尿病患者血清 HMGB1 水平、主要炎症细胞因子与颈内动脉狭窄及不稳定斑块之间的关系。
我们研究了 873 例糖尿病患者，包括 347 例行颈动脉内膜切除术的颈内动脉狭窄（ICAS）患者和 526 例无颈内动脉狭窄（WICAS）的糖尿病患者。在基线时，评估了 HMGB1 和主要炎症细胞因子的血清水平。对于 ICAS 患者，还收集了颈动脉斑块的组织学特征，以区分稳定或不稳定的动脉粥样硬化病变患者。
我们发现，与糖尿病 WICAS 患者相比，糖尿病 ICAS 患者的血清 HMGB1 水平、骨保护素、高敏 C 反应蛋白、肿瘤坏死因子-α和白细胞介素-6 显著升高。在 ICAS 患者中，不稳定斑块患者的这些细胞因子水平高于稳定斑块患者。多变量逐步逻辑回归分析显示，HMGB1 和骨保护素与 ICAS 患者的不稳定斑块独立相关。
本研究表明，在意大利糖尿病人群中，HMGB1 是颈动脉斑块易损性的独立危险因素，是颈动脉斑块不稳定的有前途的生物标志物，也是治疗不稳定颈动脉斑块和预防中风的潜在分子靶点。
