Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion.

Autores de INCLIVA
Grupos y Plataformas de I+D+i
Abstract
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- (TNF)-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 TNF 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.
© 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/)
Datos de la publicación
- ISSN/ISSNe:
- 2077-0383, 2077-0383
- Tipo:
- Article
- Páginas:
- 708-708
- DOI:
- 10.3390/jcm8050708
- PubMed:
- 31109070
Journal of Clinical Medicine MDPI
Citas Recibidas en Web of Science: 33
Documentos
Filiaciones
Keywords
- metabolic syndrome; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation
Financiación
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Cita
Marques P,Collado A,Martinez S,Domingo E,Benito E,Piqueras L,Real JT,Ascaso JF,Sanz M. Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion. J. Clin. Med. 2019. 8. (5):p. 708-708. IF:3,303. (1).
Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion. Marques P, Collado A, Martinez S, Domingo E, Benito E, Piqueras L, Real JT et al. Journal of Clinical Medicine. 2019 mayo 18. 8 (5):708-708. DOI:10.3390/jcm8050708. PMID:31109070.