Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs

The shear-responsive transcription factor Krüppel-like factor 2 (KLF2) is a critical regulator of endothelial gene expression patterns induced by atheroprotective flow. As microRNAs (miRNAs) post-transcriptionally control gene expression in many pathogenic and physiological processes, we investigated the regulation of miRNAs by KLF2 in endothelial cells. KLF2 binds to the promoter and induces a significant upregulation of the miR-143/145 cluster. Interestingly, miR-143/145 has been shown to control smooth muscle cell (SMC) phenotypes; therefore, we investigated the possibility of transport of these miRNAs between endothelial cells and SMCs. Indeed, extracellular vesicles secreted by KLF2-transduced or shear-stress-stimulated HUVECs are enriched in miR-143/145 and control target gene expression in co-cultured SMCs. Extracellular vesicles derived from KLF2-expressing endothelial cells also reduced atherosclerotic lesion formation in the aorta of ApoE(-/-) mice. Combined, our results show that atheroprotective stimuli induce communication between endothelial cells and SMCs through an miRNA- and extracellular-vesicle-mediated mechanism and that this may comprise a promising strategy to combat atherosclerosis

Metabolic homeostasis is maintained in myocardial hibernation by adaptive changes in the transcriptome and proteome

AbstractA transgenic mouse model for conditional induction of long-term hibernation via myocardium-specific expression of a VEGF-sequestering soluble receptor allowed the dissection of the hibernation process into an initiation and a maintenance phase. The hypoxic initiation phase was characterized by peak levels of K(ATP) channel and glucose transporter 1 (GLUT1) expression. Glibenclamide, an inhibitor of K(ATP) channels, blocked GLUT1 induction. In the maintenance phase, tissue hypoxia and GLUT1 expression were reduced. Thus, we employed a combined “-omics” approach to resolve this cardioprotective adaptation process. Unguided bioinformatics analysis on the transcriptomic, proteomic and metabolomic datasets confirmed that anaerobic glycolysis was affected and that the observed enzymatic changes in cardiac metabolism were directly linked to hypoxia-inducible factor (HIF)-1 activation. Although metabolite concentrations were kept relatively constant, the combination of the proteomic and transcriptomic dataset improved the statistical confidence of the pathway analysis by 2 orders of magnitude. Importantly, proteomics revealed a reduced phosphorylation state of myosin light chain 2 and cardiac troponin I within the contractile apparatus of hibernating hearts in the absence of changes in protein abundance. Our study demonstrates how combining different “-omics” datasets aids in the identification of key biological pathways: chronic hypoxia resulted in a pronounced adaptive response at the transcript and the protein level to keep metabolite levels steady. This preservation of metabolic homeostasis is likely to contribute to the long-term survival of the hibernating myocardium

Determination of the number of J/ψ events with inclusive J/ψ decays

A measurement of the number of J/ψ events collected with the BESIII detector in 2009 and 2012 is performed using inclusive decays of the J/ψ. The number of J/ψ events taken in 2009 is recalculated to be (223.7 ± 1.4) × 106, which is in good agreement with the previous measurement, but with significantly improved precision due to improvements in the BESIII software. The number of J/ψ events taken in 2012 is determined to be (1086.9 ± 6.0) × 106. In total, the number of J/ψ events collected with the BESIII detector is measured to be (1310.6 ± 7.0) × 106, where the uncertainty is dominated by systematic effects and the statistical uncertainty is negligible

Measurements of the center-of-mass energies at BESIII via the di-muon process

From 2011 to 2014, the BESIII experiment collected about 5 fb-1 data at center-of-mass energies around 4 GeV for the studies of the charmonium-like and higher excited charmonium states. By analyzing the di-muon process e+e- → γISR/FSRμ+μ-, the center-of-mass energies of the data samples are measured with a precision of 0.8 MeV. The center-of-mass energy is found to be stable for most of the time during data taking