Portal de investigación
Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Domingo, E
- Perello, E
Grupos y Plataformas de I+D+i
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- (TNF)-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, CX(3)CL1, 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.
© 2018 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:
- -
- DOI:
- 10.3390/jcm8010018
- PubMed:
- 30583563
Journal of Clinical Medicine MDPI
Citas Recibidas en Web of Science: 22
Documentos
Filiaciones
Keywords
- primary hypercholesterolemia; cytokines; chemokines; leukocyte activation; platelet activation; endothelial dysfunction; systemic inflammation
Financiación
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Cita
Collado A,Marques P,Domingo E,Perello E,Gonzalez H,Martinez S,Real JT,Piqueras L,Ascaso JF,Sanz MJ. 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. (1):18. IF:3,303. (1).
Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation. Collado A, Marques P, Domingo E, Perello E, Gonzalez H, Martinez S, Real JT et al. Journal of Clinical Medicine. 2019 enero 01. 8 (1):DOI:10.3390/jcm8010018. PMID:30583563.
