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

BACKGROUND: 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...

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Autores principales: Biscetti, Federico, Tinelli, Giovanni, Rando, Maria Margherita, Nardella, Elisabetta, Cecchini, Andrea Leonardo, Angelini, Flavia, Straface, Giuseppe, Filipponi, Marco, Arena, Vincenzo, Pitocco, Dario, Gasbarrini, Antonio, Massetti, Massimo, Flex, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161555/
https://www.ncbi.nlm.nih.gov/pubmed/34044825
http://dx.doi.org/10.1186/s12933-021-01304-8
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author Biscetti, Federico
Tinelli, Giovanni
Rando, Maria Margherita
Nardella, Elisabetta
Cecchini, Andrea Leonardo
Angelini, Flavia
Straface, Giuseppe
Filipponi, Marco
Arena, Vincenzo
Pitocco, Dario
Gasbarrini, Antonio
Massetti, Massimo
Flex, Andrea
author_facet Biscetti, Federico
Tinelli, Giovanni
Rando, Maria Margherita
Nardella, Elisabetta
Cecchini, Andrea Leonardo
Angelini, Flavia
Straface, Giuseppe
Filipponi, Marco
Arena, Vincenzo
Pitocco, Dario
Gasbarrini, Antonio
Massetti, Massimo
Flex, Andrea
author_sort Biscetti, Federico
collection PubMed
description BACKGROUND: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-81615552021-06-01 Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population Biscetti, Federico Tinelli, Giovanni Rando, Maria Margherita Nardella, Elisabetta Cecchini, Andrea Leonardo Angelini, Flavia Straface, Giuseppe Filipponi, Marco Arena, Vincenzo Pitocco, Dario Gasbarrini, Antonio Massetti, Massimo Flex, Andrea Cardiovasc Diabetol Original Investigation BACKGROUND: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2021-05-27 /pmc/articles/PMC8161555/ /pubmed/34044825 http://dx.doi.org/10.1186/s12933-021-01304-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Original Investigation
Biscetti, Federico
Tinelli, Giovanni
Rando, Maria Margherita
Nardella, Elisabetta
Cecchini, Andrea Leonardo
Angelini, Flavia
Straface, Giuseppe
Filipponi, Marco
Arena, Vincenzo
Pitocco, Dario
Gasbarrini, Antonio
Massetti, Massimo
Flex, Andrea
Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
title Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
title_full Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
title_fullStr Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
title_full_unstemmed Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
title_short Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
title_sort association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161555/
https://www.ncbi.nlm.nih.gov/pubmed/34044825
http://dx.doi.org/10.1186/s12933-021-01304-8
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