Background-Platelets participate in events that immediately precede acute myocardial infarction. Because platelets lack nuclear DNA but retain megakaryocyte-derived mRNAs, the platelet transcriptome provides a novel window on gene expression preceding acute coronary events. Methods and Results-We profiled platelet mRNA from patients with acute ST-segment-elevation myocardial infarction (STEMI, nϭ16) or stable coronary artery disease (nϭ44). The platelet transcriptomes were analyzed and single-gene models constructed to identify candidate genes with differential expression. We validated 1 candidate gene product by performing a prospective, nested case-control study (nϭ255 case-control pairs) among apparently healthy women to assess the risk of future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) associated with baseline plasma levels of the candidate protein. Platelets isolated from STEMI and coronary artery disease patients contained 54 differentially expressed transcripts. The strongest discriminators of STEMI in the microarrays were CD69 (odds ratio 6.2, PϽ0.001) and myeloid-related protein-14 (MRP-14; odds ratio 3.3, Pϭ0.002). Plasma levels of MRP-8/14 heterodimer were higher in STEMI patients (17.0 versus 8.0 g/mL, PϽ0.001). In the validation study, the risk of a first cardiovascular event increased with each increasing quartile of MRP-8/14 (P trend Ͻ0.001) such that women with the highest levels had a 3.8-fold increase in risk of any vascular event (PϽ0.001).Risks were independent of standard risk factors and C-reactive protein. Conclusions-The

The RV FDG accumulation corrected for the partial volume effect was significantly increased in accordance with the severity of the RV pressure overload (i.e., the RV peak-systolic wall stress) in patients with pulmonary hypertension. Furthermore, the corrected RV FDG accumulation was decreased after the treatment with epoprostenol in accordance with the degree of reduction in the pulmonary vascular resistance and RV peak-systolic wall stress.

Background— Myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) are members of the S100 family of calcium-modulated proteins that regulate myeloid cell function and control inflammation, in part, through activation of Toll-like receptor-4 and the receptor for advanced glycation end products. A transcriptional profiling approach in patients with acute coronary syndromes identified MRP-14 as a novel predictor of myocardial infarction. Further studies demonstrated that elevated plasma levels of MRP-8/14 heterodimer predict increased risk of first and recurrent cardiovascular events. Beyond its serving as a risk marker, whether MRP-8/14 participates directly in vascular inflammation and disease remains unclear. Methods and Results— We evaluated vascular inflammation in wild-type and MRP-14 –deficient ( MRP-14 −/− ) mice that lack MRP-8/14 complexes with experimental arterial injury, vasculitis, or atherosclerosis. After femoral artery wire injury, MRP-14 −/− mice had significant reductions in leukocyte accumulation, cellular proliferation, and neointimal formation compared with wild-type mice. In a cytokine-induced local Shwartzman-like reaction that produces thrombohemorrhagic vasculitis, MRP-14 −/− mice had significant reductions in neutrophil accumulation, lesion severity, and hemorrhagic area. In response to high-fat feeding, mice doubly deficient in apolipoprotein E and MRP-8/14 complexes had attenuation in atherosclerotic lesion area and in macrophage accumulation in plaques compared with mice deficient in apolipoprotein E alone. Conclusion— This study demonstrates that MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.

This study demonstrates that GP Ibalpha is a physiologically relevant ligand for alphaMbeta2 and that integrin engagement of GP Ibalpha is critical to leukocyte function and the biological response to vascular injury. These observations establish a molecular target for selectively disrupting leukocyte-platelet complexes that promote inflammation in thrombosis and restenosis.

Background-Using a transcriptional profiling approach, we recently identified myeloid-related protein-8/14 (MRP-8/14) to be expressed by platelets during acute MI. Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals, but have not been assessed with respect to prognosis in patients with ACS.

The cellular and molecular processes that control vascular injury responses following PCI involve a complex interplay among vascular cells and progenitor cells that control arterial remodeling, neoinitimal proliferation and reendothelialization. Drug eluting stents (DES) improve the efficacy of peructaneous coronary intervention (PCI) by modulating vascular inflammation and preventing neointimal proliferation and restenosis. Although positive effects of DES reduce inflammation and restenosis, negative effects delay reendothelialization and impair endothelial function. Delayed reendothelialization and impaired endothelial function may be linked to stent thrombosis and adverse clinical outcomes following DES use. Compared with BMS, DES may also differentially modulate mobilization, homing and differentiation of vascular progenitor cells involved reendothelialization and neointimal proliferation. The effects of DES on vascular inflammation and repair directly impact clinical outcomes with these devices and dictate requirements for extended duration dual antiplatelet therapy.

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SummaryBackground: Although the incidence of acute pulmonary thromboembolism (APTE) has been increasing in Japan, patient characteristics, management strategies, and outcome