Next Article in Journal
Dietary Profiles, Nutritional Biochemistry Status, and Attention-Deficit/Hyperactivity Disorder: Path Analysis for a Case-Control Study
Previous Article in Journal
Bone Marrow Adipocytes: The Enigmatic Components of the Hematopoietic Stem Cell Niche
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

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
Received: 15 April 2019 / Revised: 14 May 2019 / Accepted: 16 May 2019 / Published: 18 May 2019
(This article belongs to the Section Endocrinology & Metabolism)
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. View Full-Text
Keywords: metabolic syndrome; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation metabolic syndrome; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation
Show Figures

Graphical abstract

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.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop