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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Increased levels of circulating platelet-derived microparticles in psoriasis: Possible implications for the associated cardiovascular risk
Evangelia Papadavid, Konstantina Diamanti, Aris Spathis, Maria Varoudi, Ioanna Andreadou, Kostas Gravanis, Kostas Theodoropoulos, Petros Karakitsos, John Lekakis, Dimitrios Rigopoulos, Ignatios Ikonomidis
Evangelia Papadavid, Konstantina Diamanti, Kostas Theodoropoulos, Dimitrios Rigopoulos, 2nd Department of Dermatology and Venereology, University of Athens Medical School, Attikon Hospital, 12462 Athens, Greece
Aris Spathis, Petros Karakitsos, Department of Cytopathology, University of Athens Medical School, Attikon Hospital, 12462 Athens, Greece
Maria Varoudi, John Lekakis, Ignatios Ikonomidis, 2nd Department of Cardiology, University of Athens Medical School, Attikon Hospital, 12462 Athens, Greece
Ioanna Andreadou, Kostas Gravanis, Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, 15771 Athens, Greece
Author contributions: Papadavid E, Diamanti K and Spathis A contributed equally to this work; Diamanti K conceived the research; Papadavid E, Diamanti K and Ikonomidis I designed the study; Papadavid E, Diamanti K, Varoudi M, Theodoropoulos K and Ikonomidis I contributed to data acquisition; Spathis A, Andreadou I, Gravanis K and Ikonomidis I participated in data analysis and interpretation; Diamanti K wrote the article; Papadavid E, Karakitsos P, Lekakis J, Rigopoulos D and Ikonomidis I revised the article critically for important intellectual content.
Institutional review board statement: The study was reviewed and approved by the Attikon University Hospital Institutional Review Board, conducted in compliance with the Declaration of Helsinki.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the contributing authors of the present manuscript declare that they have no conflict of interest to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at ignoik@otenet.gr. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ignatios Ikonomidis, MD, FESC, 2nd Department of Cardiology, University of Athens Medical School, Attikon Hospital, Rimini 1, Haidari, 12462 Athens, Greece. ignoik@otenet.gr
Telephone: +30-210-5832187 Fax: +30-210-5832351
Received: June 28, 2016
Peer-review started: July 1, 2016
First decision: August 5, 2016
Revised: August 20, 2016
Accepted: September 7, 2016
Article in press: September 8, 2016
Published online: November 26, 2016
AIM
To evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of psoriasis.
METHODS
Forty psoriatic patients without cardiovascular disease, and 12 healthy controls were subjected to measurement of baseline platelet CD62P, CD63 and CD42b expression, platelet-leukocyte complexes, i.e., platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC) and platelet-lymphocyte complexes, and concentrations of platelet-derived microparticles (PMPs) using flow cytometry. Both larger-size (0.5-0.9 μm) and smaller-size (< 0.5 μm) PMPs were determined. Serum interleukin (IL)-12 and IL-17 levels were also measured by enzyme-linked immunosorbent assay. The severity of psoriasis was evaluated by the Psoriasis Area Severity Index (PASI).
RESULTS
PMP concentrations were significantly higher in psoriasis patients than controls [mean ± standard error of mean (SEM): 22 ± 5/μL vs 11 ± 6/μL; P = 0.018), for both smaller-size (10 ± 2/μL vs 4 ± 2/μL; P = 0.033) and larger-size (12 ± 3/μL vs 6 ± 4/μL; P = 0.014) PMPs. Platelet CD62P, CD63 and CD42b expression and circulating PMC and PNC were similar between the two groups. Lower circulating PLC were observed in psoriasis patients compared to controls (mean ± SEM: 16% ± 3% vs 23% ± 6%; P = 0.047). Larger-size PMPs were related with IL-12 levels (P < 0.001) and smaller-size PMPs with both IL-12 and IL-17 levels (P < 0.001). Total PMPs also correlated with IL-12 (P < 0.001). CD63 expression was positively correlated with both IL-12 and IL-17 (P < 0.05). Increased PASI score was associated with increased levels of larger-size PMPs (r = 0.45; P = 0.011) and increased CD63 expression (r = 0.47; P < 0.01).
CONCLUSION
PMPs, known to be predictive of cardiovascular outcomes, are increased in psoriasis patients, and associated with high inflammatory disease burden. Enhanced platelet activation may be the missing link leading to cardiovascular events in psoriatic patients.
Core tip: Psoriasis is associated with increased risk of cardiovascular disease. The pathogenic mechanisms shared by the two diseases seem to converge onto “inflammation” phenomenon. Platelets have a potent role in inflammation. Herein we evaluated platelet activation in psoriasis patients compared to healthy controls, and investigated a potential association between platelet activation markers and the inflammatory burden of psoriasis, the latter assessed by serum levels of pivotal pro-inflammatory cytokines implicated in psoriasis. We conclude that the association between psoriasis and atherosclerosis may be related to excessive platelet-derived microparticles (PMPs) formation. The size class of PMPs was taken into consideration in our study.
