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Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion

Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CX(3)CL1/CX(3)CR1 and CCL2/CCR2 chemokine axes. M...

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Autores principales: Marques, Patrice, Collado, Aida, Martinez-Hervás, Sergio, Domingo, Elena, Benito, Esther, Piqueras, Laura, Real, José T., Ascaso, Juan F., Sanz, Maria-Jesus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572270/
https://www.ncbi.nlm.nih.gov/pubmed/31109070
http://dx.doi.org/10.3390/jcm8050708
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author Marques, Patrice
Collado, Aida
Martinez-Hervás, Sergio
Domingo, Elena
Benito, Esther
Piqueras, Laura
Real, José T.
Ascaso, Juan F.
Sanz, Maria-Jesus
author_facet Marques, Patrice
Collado, Aida
Martinez-Hervás, Sergio
Domingo, Elena
Benito, Esther
Piqueras, Laura
Real, José T.
Ascaso, Juan F.
Sanz, Maria-Jesus
author_sort Marques, Patrice
collection PubMed
description Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CX(3)CL1/CX(3)CR1 and CCL2/CCR2 chemokine axes. Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CX(3)CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium and the role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 axes was investigated with the parallel-plate flow chamber. Results: When compared with the controls, the metabolic syndrome patients presented greater percentages of eosinophils, CD3(+) T lymphocytes, Mon2/Mon3 monocytes, platelet-eosinophil and -lymphocyte aggregates, activated platelets, neutrophils, eosinophils, monocytes, and CD8(+) T cells, but lower percentages of Mon1 monocytes. Patients had increased circulating interleukin-8 (IL-8) and TNFα levels and decreased IL-4. CX(3)CR1 up-regulation in platelet-Mon1 monocyte aggregates in metabolic syndrome patients led to increased CX(3)CR1/CCR2-dependent platelet-Mon1 monocyte adhesion to dysfunctional arterial endothelium. Conclusion: We provide evidence of generalized immune activation in metabolic syndrome. Additionally, CX(3)CL1/CX(3)CR1 or CCL2/CCR2 axes are potential candidates for therapeutic intervention in cardiovascular disorders in metabolic syndrome patients, as their blockade impairs the augmented arterial platelet-Mon1 monocyte aggregate adhesiveness, which is a key event in atherogenesis.
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spelling pubmed-65722702019-06-18 Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion Marques, Patrice Collado, Aida Martinez-Hervás, Sergio Domingo, Elena Benito, Esther Piqueras, Laura Real, José T. Ascaso, Juan F. Sanz, Maria-Jesus J Clin Med Article Background: Metabolic syndrome is associated with low-grade systemic inflammation, which is a key driver of premature atherosclerosis. We characterized immune cell behavior in metabolic syndrome, its consequences, and the potential involvement of the CX(3)CL1/CX(3)CR1 and CCL2/CCR2 chemokine axes. Methods: Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, activation, platelet-leukocyte aggregates, and CX(3)CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium and the role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 axes was investigated with the parallel-plate flow chamber. Results: When compared with the controls, the metabolic syndrome patients presented greater percentages of eosinophils, CD3(+) T lymphocytes, Mon2/Mon3 monocytes, platelet-eosinophil and -lymphocyte aggregates, activated platelets, neutrophils, eosinophils, monocytes, and CD8(+) T cells, but lower percentages of Mon1 monocytes. Patients had increased circulating interleukin-8 (IL-8) and TNFα levels and decreased IL-4. CX(3)CR1 up-regulation in platelet-Mon1 monocyte aggregates in metabolic syndrome patients led to increased CX(3)CR1/CCR2-dependent platelet-Mon1 monocyte adhesion to dysfunctional arterial endothelium. Conclusion: We provide evidence of generalized immune activation in metabolic syndrome. Additionally, CX(3)CL1/CX(3)CR1 or CCL2/CCR2 axes are potential candidates for therapeutic intervention in cardiovascular disorders in metabolic syndrome patients, as their blockade impairs the augmented arterial platelet-Mon1 monocyte aggregate adhesiveness, which is a key event in atherogenesis. MDPI 2019-05-18 /pmc/articles/PMC6572270/ /pubmed/31109070 http://dx.doi.org/10.3390/jcm8050708 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marques, Patrice
Collado, Aida
Martinez-Hervás, Sergio
Domingo, Elena
Benito, Esther
Piqueras, Laura
Real, José T.
Ascaso, Juan F.
Sanz, Maria-Jesus
Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
title Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
title_full Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
title_fullStr Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
title_full_unstemmed Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
title_short Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX(3)CL1/CX(3)CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion
title_sort systemic inflammation in metabolic syndrome: increased platelet and leukocyte activation, and key role of cx(3)cl1/cx(3)cr1 and ccl2/ccr2 axes in arterial platelet-proinflammatory monocyte adhesion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572270/
https://www.ncbi.nlm.nih.gov/pubmed/31109070
http://dx.doi.org/10.3390/jcm8050708
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