Dataset Information

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.

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 CX₃CL1/CX₃CR1 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 CX₃CR1 expression. ELISA determined the plasma marker levels. Platelet-leukocyte aggregates adhesion to tumor necrosis factor-? (TNF?)-stimulated arterial endothelium and the role of CX₃CL1/CX₃CR1 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. CX₃CR1 up-regulation in platelet-Mon1 monocyte aggregates in metabolic syndrome patients led to increased CX₃CR1/CCR2-dependent platelet-Mon1 monocyte adhesion to dysfunctional arterial endothelium.

Conclusion

We provide evidence of generalized immune activation in metabolic syndrome. Additionally, CX₃CL1/CX₃CR1 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.

SUBMITTER: Marques P

PROVIDER: S-EPMC6572270 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

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

Marques Patrice P Collado Aida A Martinez-Hervás Sergio S Domingo Elena E Benito Esther E Piqueras Laura L Real José T JT Ascaso Juan F JF Sanz Maria-Jesus MJ

Journal of clinical medicine 20190518 5

<h4>Background</h4>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<sub>3</sub>CL1/CX<sub>3</sub>CR1 and CCL2/CCR2 chemokine axes.<h4>Methods</h4>Whole blood from 18 patients with metabolic syndrome and 21 age-matched controls was analyzed by flow cytometry to determine the leukocyte immunophenotypes, acti ...[more]

PMID: 31109070

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