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J. Clin. Med. 2019, 8(1), 18; https://doi.org/10.3390/jcm8010018

Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation

1
Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain
2
Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain
3
Institute of Health Research of the University Clinic Hospital of Valencia (INCLIVA), Av. Menéndez Pelayo 4, 46010 Valencia, Spain
4
Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Institute of Health Carlos III (ISCIII), Av. Monforte de Lemos 3-5, 28029 Madrid, Spain
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 19 November 2018 / Revised: 14 December 2018 / Accepted: 19 December 2018 / Published: 22 December 2018
(This article belongs to the Section Endocrinology & Metabolism)
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Abstract

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium was investigated using the dynamic model of the parallel-plate flow chamber. PH patients presented greater percentage of Mon 3 monocytes, Th2 and Th17 lymphocytes, activated platelets, and leukocytes than controls. The higher percentages of circulating platelet-neutrophil, monocyte and lymphocyte aggregates in patients caused increased platelet-leukocyte adhesion to dysfunctional arterial endothelium. Circulating CXCL8, CCL2, CX3CL1, and IL-6 levels positively correlated with key lipid features of PH, whereas negative correlations were found for IL-4 and IL-10. We provide the first evidence that increased platelet and leukocyte activation leads to elevated platelet-leukocyte aggregates in PH and augmented arterial leukocyte adhesiveness, a key event in atherogenesis. Accordingly, modulation of immune system behavior might be a powerful target in the control of further cardiovascular disease in PH. View Full-Text
Keywords: primary hypercholesterolemia; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation primary hypercholesterolemia; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Collado, A.; Marques, P.; Domingo, E.; Perello, E.; González-Navarro, H.; Martinez-Hervás, S.; Real, J.T.; Piqueras, L.; Ascaso, J.F.; Sanz, M.-J. Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation. J. Clin. Med. 2019, 8, 18.

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