Abstract
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.
Highlights
Carotid atherosclerosis represents one of the complications of diabetes mellitus
We found that High mobility group box-1 (HMGB1) serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic internal carotid artery stenosis (ICAS) patients compared to diabetic without internal carotid artery stenosis (WICAS) 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
Summary
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. Biscetti et al Cardiovasc Diabetol (2021) 20:114 development and vulnerability [5, 6] and several studies have analyzed the linkage between carotid atherosclerosis and inflammatory biomarkers, such as high-sensitivity C-reactive protein (Hs-CRP), interleukin (IL)-6, serum amyloid A, fibrinogen, lipoprotein-associated phospholipase A2 (Lp-PLA2) [6,7,8,9,10,11,12]. High mobility group box-1 (HMGB1) is a DNA-binding protein, which acts in the extracellular space as a pro-inflammatory cytokine [13], promoting inflammatory response, tissue regeneration and angiogenesis [14, 15]. HMGB1 acts by linking to the toll-like receptors and advanced glycation end product receptors, enhancing the inflammatory response, chemotaxis, immune and endothelial cells activation and differentiation [14]
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