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Background: Circulating microRNAs (miRNAs) emerge as novel biomarkers in cardiovascular diseases. Diagnosing acute pulmonary embolism (PE) remains challenging due to a diverse clinical presentation and the lack of specific biomarkers. Here we evaluate serum miRNAs as potential biomarkers in acute PE.Methods: We enrolled 30 patients with acute, CT (computed tomography)-angiographically confirmed central PE and collected serum samples on the day of emergency room admission (1st day) and from 22 of these patients 9 months thereafter. For comparison, we examined serum samples from patients with acute non ST-segment elevation myocardial infarction (NSTEMI, n = 30) and healthy individuals (n = 12).Results: We randomly selected 16 out of 30 PE patients and screened sera from the acute (1st day) and chronic stages (9 months) for 754 miRNAs using microarrays and found 37 miRNAs to be differentially regulated. Across all miRNAs, miRNA-1233 displayed the highest fold change (FC) from acute to chronic stage (log2FC 11.5, p < 0.004). We validated miRNA-1233 by real-time quantitative polymerase chain reaction (RT-qPCR). In acute PE (1st day) we found elevated levels of miRNA-1233 in comparison to NSTEMI (log2FC 5.7, p < 0.0001) and healthy controls (log2FC 7.7, p < 0.0001). miRNA-1233 differentiated acute PE from NSTEMI patients and healthy individuals with 90 and 90 % sensitivity, and 100 and 92 % specificity [area under the curve (AUC) 0.95, p < 0.001 and 0.91, p < 0.001], respectively.Conclusions: This is the first report that identifies a miRNA that allows distinguishing acute PE from acute NSTEMI and healthy individuals with high specificity and sensitivity. [ABSTRACT FROM AUTHOR]

Background: The involvement of collateral blood flow/fluid shear stress, nitric oxide (NO), and macrophages during collateral growth (arteriogenesis) is established, but their interplay remains paradoxical., Methods: In order to further elucidate the "fluid shear stress/NO/macrophage" paradox, we investigated the time course of collateral blood flow (using a Doppler flow probe) and NOS expression (immunohistochemistry, Western blot) in growing rat collateral vessels after femoral artery occlusion and their impact on macrophage recruitment and collateral proliferation (immunohistochemistry, angiographies)., Results: (values are given as mean ± standard error of mean) Early after occlusion, collateral blood flow was significantly reduced (pre- 90.0 ± 4.5 vs. post-occlusion 62.5 ± 5.9 μl/min; p < 0.01), and local inducible NOS (iNOS) and endothelial NOS (eNOS) expression were down-regulated (expression in % of non-occluded: eNOS 49.4 ± 11.8% and iNOS 54.5 ± 7.9% vs. non-occluded at 12 h after occlusion; p < 0.03). An artificial rise (induced by a peripheral vasodilatation) of the initially decreased collateral blood flow back to pre-occlusion levels reduced collateral macrophage recruitment (macrophages per collateral section: post- 42.5 ± 4.4 vs. artificial pre-occlusion 27.8 ± 2.0; p < 0.05) and diminished collateral proliferation (proliferative index: post- 0.54 ± 0.02 vs. artificial pre-occlusion 0.19 ± 0.04; p < 0.001) significantly 72 h after femoral artery occlusion., Conclusions: We propose the following resolution of the "fluid shear stress/NO/macrophage" paradox: Collateral blood flow and NOS expression are initially reduced during arteriogenesis allowing macrophages to accumulate and therewith enhancing collateral proliferation. After homing of macrophages (24 h after occlusion), collateral blood flow and NOS expression recover in order to join the effects of macrophages for restoring blood flow.