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

Abstract

AIMTo evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of psoriasis.METHODSForty 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).RESULTSPMP 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).CONCLUSIONPMPs, 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.

<p>Biomarkers of subclinical atherosclerosis in patients with psoriatic arthritis</p>

“…CRP values were lower in subjects with MDA than in those with active disease, and directly correlated with max-A%. Platelet hyperreactivity is a major predictor of cardiovascular events and of arterial thrombosis,74 and these findings strongly support a synergism between inflammation and pathobiology of atherothrombosis 78. Moreover, the study by Di Minno et al showed that platelet function is increased in patients with PsA, especially in those with poorly controlled disease 13,82.…”

“…Platelets produce inflammatory mediators and mediate leukocyte incorporation into plaques through platelet-mediated leukocyte adhesion. Pathomechanisms of psoriasis imply platelet activation, mediated by chronic inflammation 75–78. Psoriatic patients show high titers of serum platelet-derived microparticles and P-selectin, which are both markers of platelet hyperreactivity, as reported by several studies 76–78…”

Psoriasis and Cardiovascular Comorbidities: Focusing on Severe Vascular Events, Cardiovascular Risk Factors and Implications for Treatment

“…They may be released as a result of cell activation or apoptosis, and are involved in the development of atherosclerosis [ 227 ]. Previous studies have shown that psoriasis patients have increased blood levels of microparticles, which may contribute to the development of atherosclerosis and cardiovascular comorbidities [ 228 , 229 , 230 ].…”

Role of Microparticles in the Pathogenesis of Inflammatory Joint Diseases

“…An increase in the number of circulating endothelial, platelet, and monocyte-derived MPs in psoriatic patients was also observed in a study conducted by Takeshita et al [9]. In another paper, Papadavid et al described a considerable increase in the number of PMPs correlating with an increase in the concentration of interleukin 12 (IL-12) and an increase in the disease activity as assessed by the PASI (Psoriasis Area Severity Index) [83]. In another study with patients with severe psoriasis (with or without psoriatic arthritis), Ho et al observed a larger number of circulating PMPs and EMPs in patients compared with the control group [47].…”