Plasma signature of apoptotic microvesicles is associated with endothelial dysfunction and plaque rupture in acute coronary syndromes.

OBJECTIVE: Circulating microvesicles (MV) are surrogate biomarkers of atherosclerosis. However, their role in acute coronary syndromes (ACS) has not been fully elucidated yet. We sought to examine the association of circulating apoptotic MVs with ACS pathophysiology. APPROACH AND RESULTS: One hundred and fifty-three patients (n = 153) were included in the study; 49 patients with ST-elevation myocardial infarction (STEMI), 35 with non-STEMI (NSTEMI), 38 with unstable angina, 15 with stable coronary artery disease and 16 control individuals. Flow cytometry analysis was used to quantify circulating apoptotic/non-apoptotic (phospatidyloserine+/phospatidyloserine-) endothelial cell (EMV), red blood cell (RMV) and platelet (PMV) derived MV. Flow-mediated dilatation (FMD) of the brachial artery was assessed by ultrasound to estimate endothelial function. The inflammatory profile was assessed by serum C-reactive protein (hsCRP) levels. Apoptotic only (but not non-apoptotic) MV were increased in patients with ACS (EMV, P = 2.32 × 10-9; RMV, P = .0019; PMV, P = .01). Hierarchical clustering of the total population of ACS patients (n = 122) by circulating levels of phospatidyloserine+ EMV, RMV and PMV identified two discreet clusters of patients without any differences in traditional risk factors, but significant differences in brachial FMD (5.2% (2.5) vs. 4.1% (2.3), P < .05) that remained significant after adjustment for co-variates. The prevalence of STEMI, a surrogate for plaque rupture and vessel thrombotic occlusion, was significantly higher in the patient cluster with impaired endothelial function (60% vs 32%, P = .016, adjusted odds ratio for STEMI, 3.041, 95%CI, 1.160 to 7.968, p = .024). CONCLUSION: Our findings indicate that the circulating levels of apoptotic MV are increased in ACS patients and their plasma profiles associate with endothelial dysfunction and thrombotic complications in ACS patients.

Cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children with obstructive sleep apnea.

OBJECTIVES: Cysteinyl leukotrienes have been implicated in the pathogenesis of adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). This study aimed to quantify the expression of cysteinyl leukotriene receptors (CysLT(1), CysLT(2)) by tonsillar lymphocyte subpopulations from children with OSA and to make comparisons to lymphocyte subpopulations from control subjects with recurrent tonsillitis (RT). METHODS: Tonsillar tissue from children with OSA or RT was studied for CysLT(1) and CysLT(2) expression by RT-PCR, flow cytometry (FC), and immunofluorescence. RESULTS: Ten children with OSA and 10 control subjects were recruited. In OSA participants, CysLT(1)+ fraction of small-size CD19+ B-lymphocytes was similar to the CysLT(1)+ CD3+ T-lymphocytes fraction (FC: 36.5 [16.5-55.4] vs. 14 [2.8-22.1]) (p>0.05) and higher than the CysLT(1)+ moderate/large-size CD19+ B-lymphocytes fraction (6.6 [1.5-14.4]) (p<0.01). Similar trends were recognized for CysLT(2). CysLT(1) and CysLT(2) immunoreactivity was detected by immunofluorescence in the tonsillar mantle zones (small B-lymphocytes) and the extrafollicular areas (T-lymphocytes). Compared to subjects with RT, children with OSA had significantly higher expression of CysLT(1) in small-size CD19+ B-lymphocytes (FC) and in CD3+ T-lymphocytes (RT-PCR and FC) (p<0.05). CONCLUSIONS: Increased expression of leukotriene receptors by immunologically active tonsillar areas in children with OSA is a potential therapeutic target for pediatric sleep apnea.