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      Increased levels of circulating platelet-derived microparticles in psoriasis: Possible implications for the associated cardiovascular risk

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          Abstract

          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.

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          Most cited references 42

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          Psoriasis.

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            Risk of myocardial infarction in patients with psoriasis.

            Psoriasis is the most common T-helper cell type 1 (T(H)1) immunological disease. Evidence has linked T(H)1 diseases to myocardial infarction (MI). Psoriasis has been associated with cardiovascular diseases, but has only been investigated in hospital-based studies that did not control for major cardiovascular risk factors. To determine if within a population-based cohort psoriasis is an independent risk factor for MI when controlling for major cardiovascular risk factors. A prospective, population-based cohort study in the United Kingdom of patients with psoriasis aged 20 to 90 years, comparing outcomes among patients with and without a diagnosis of psoriasis. Data were collected by general practitioners as part of the patient's medical record and stored in the General Practice Research Database between 1987 and 2002, with a mean follow-up of 5.4 years. Adjustments were made for hypertension, diabetes, history of myocardial infarction, hyperlipidemia, age, sex, smoking, and body mass index. Patients with psoriasis were classified as severe if they ever received a systemic therapy. Up to 5 controls without psoriasis were randomly selected from the same practices and start dates as the patients with psoriasis. A total of 556,995 control patients and patients with mild (n = 127,139) and severe psoriasis (n = 3837) were identified. Incident MI. There were 11,194 MIs (2.0%) within the control population and 2319 (1.8%) and 112 (2.9%) MIs within the mild and severe psoriasis groups, respectively. The incidences per 1000 person-years for control patients and patients with mild and severe psoriasis were 3.58 (95% confidence interval [CI], 3.52-3.65), 4.04 (95% CI, 3.88-4.21), and 5.13 (95% CI, 4.22-6.17), respectively. Patients with psoriasis had an increased adjusted relative risk (RR) for MI that varied by age. For example, for a 30-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.29 (95% CI, 1.14-1.46) and 3.10 (95% CI, 1.98-4.86), respectively. For a 60-year-old patient with mild or severe psoriasis, the adjusted RR of having an MI is 1.08 (95% CI, 1.03-1.13) and 1.36 (95% CI, 1.13-1.64), respectively. Psoriasis may confer an independent risk of MI. The RR was greatest in young patients with severe psoriasis.
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              Microparticles in cardiovascular diseases.

              Microparticles are membrane vesicles released from many different cell types. There are two mechanisms that can result in their formation, cell activation and apoptosis. In these two mechanisms, different pathways are involved in microparticle generation. Microparticle generation seems to be a well regulated process. Microparticles vary in size, phospholipid and protein composition. They have a potent pro-inflammatory effect, promote coagulation and affect vascular function. Since these processes are all involved in the pathogenesis of cardiovascular disease and circulating microparticle numbers are altered in many cardiovascular diseases, a role for microparticles in the pathogenesis of cardiovascular diseases is likely. Although hard evidence for a role of microparticles in cardiovascular diseases at present is still only limited, new evidence is accumulating rapidly to support this theory. Elucidation of the microparticle composition and the mechanisms involved in exertion of their effects will supply this evidence and enable us to develop additional intervention strategies for prevention and treatment of cardiovascular diseases.
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                Author and article information

                Journal
                World J Cardiol
                WJC
                World Journal of Cardiology
                Baishideng Publishing Group Inc
                1949-8462
                26 November 2016
                26 November 2016
                : 8
                : 11
                : 667-675
                Affiliations
                Evangelia Papadavid, Konstantina Diamanti, Kostas Theodoropoulos, Dimitrios Rigopoulos, 2 nd 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, 2 nd 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 notes

                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.

                Correspondence to: Dr. Ignatios Ikonomidis, MD, FESC, 2 nd Department of Cardiology, University of Athens Medical School, Attikon Hospital, Rimini 1, Haidari, 12462 Athens, Greece. ignoik@ 123456otenet.gr

                Telephone: +30-210-5832187 Fax: +30-210-5832351

                Article
                jWJC.v8.i11.pg667
                10.4330/wjc.v8.i11.667
                5124725
                27957253
                ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.

                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/

                Categories
                Observational Study

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