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, Patrice; Collado, Aida; Martinez-Hervás, Sergio; Domingo, Elena; Benito, Esther; Piqueras, Laura; Real, José T.; Ascaso, Juan F.; Sanz, Maria-Jesus

doi:10.3390/jcm8050708

Open AccessArticle

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

by

Patrice Marques

^1,2,†

,

Aida Collado

^1,2,†

,

Sergio Martinez-Hervás

^2,3,4,5

,

Elena Domingo

^1,2,

Esther Benito

^2,4,5

,

Laura Piqueras

^1,2,5,

José T. Real

^2,3,4,5,

Juan F. Ascaso

^2,3,4,5,* and

Maria-Jesus Sanz

^1,2,5,*

¹

Department of Pharmacology, University of Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain

²

Institute of Health Research INCLIVA, Av. Menéndez Pelayo 4, 46010 Valencia, Spain

³

Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain

⁴

Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Av. Menéndez Pelayo 4, 46010 Valencia, Spain

⁵

CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, ISCIII, Av. Monforte de Lemos 3-5, 28029 Madrid, Spain

^*

Authors to whom correspondence should be addressed.

^†

Both authors contributed equally to this work.

J. Clin. Med. 2019, 8(5), 708; https://doi.org/10.3390/jcm8050708

Submission received: 15 April 2019 / Revised: 14 May 2019 / Accepted: 16 May 2019 / Published: 18 May 2019

(This article belongs to the Section Endocrinology & Metabolism)

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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-α (TNFα)-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 TNFα 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.

Keywords: metabolic syndrome; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation

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MDPI and ACS Style

Marques, P.; Collado, A.; Martinez-Hervás, S.; Domingo, E.; Benito, E.; Piqueras, L.; Real, J.T.; Ascaso, J.F.; Sanz, M.-J. 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, 708. https://doi.org/10.3390/jcm8050708

AMA Style

Marques P, Collado A, Martinez-Hervás S, Domingo E, Benito E, Piqueras L, Real JT, Ascaso JF, Sanz M-J. 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. Journal of Clinical Medicine. 2019; 8(5):708. https://doi.org/10.3390/jcm8050708

Chicago/Turabian Style

Marques, Patrice, Aida Collado, Sergio Martinez-Hervás, Elena Domingo, Esther Benito, Laura Piqueras, José T. Real, Juan F. Ascaso, and Maria-Jesus Sanz. 2019. "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" Journal of Clinical Medicine 8, no. 5: 708. https://doi.org/10.3390/jcm8050708

APA Style

Marques, P., Collado, A., Martinez-Hervás, S., Domingo, E., Benito, E., Piqueras, L., Real, J. T., Ascaso, J. F., & Sanz, M.-J. (2019). 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. Journal of Clinical Medicine, 8(5), 708. https://doi.org/10.3390/jcm8050708

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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

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