Abstract
Introduction
Cardiovascular disease is the major cause of death worldwide. The physiological status of the cardiovascular system is reflected in plasma proteins and a newly developed ...technique based on proximity extension assays has enabled the analysis of a broad range of protein biomarkers associated with cardiovascular disease. However, biomarkers for coronary high-risk plaques, including lipid-rich plaques, macrophages, cholesterol crystals, and microvessels, have not yet been found.
Purpose
This study aimed to identify proteins specific for coronary high-risk plaques.
Methods
We analyzed 57 patients (71.1 ± 10.6 years, male: 68.4%) who underwent intracoronary optical coherence tomography and provided blood samples for proteomic analysis. Forty-seven patients (86.0%) had lipid-rich plaques, 46 patients (80.7%) had macrophages, 16 patients (28.1%) had cholesterol crystals, and 27 patients (47.4%) had microvessels. A total of 1,470 plasma proteins were analyzed using the Olink® Explore 1,536 Reagent Kit and P2 100 cycle reagent kit on a NextSeq 2000 sequencer.
Results
In patients with lipid-rich plaques, the protein expressions of Interstitial collagenase (MMP1), Wiskott-Aldrich syndrome protein family member 1 (WASF1), and Protein phosphatase 1 regulatory subunit 12A (PPP1R12RA) were significantly increased, while the expressions of Fc receptor-like protein 3 (FCRL3), Folate receptor gamma (FOLR3), Cobalamin binding intrinsic factor (CBLIF), Glutathione S-transferase A1 (GSTA1), and Keratin, type I cytoskeletal 18 (KRT18) were significantly decreased (Figure A). In patients with macrophages, the protein expressions of MMP1, WASF1, PPP1R12RA, and Scavenger receptor cysteine-rich domain-containing group B protein (SSC4D) were significantly increased, while the expressions of Fatty acid-binding protein, intestinal (FABP2), FOLR3, CBLIF, GSTA1, and Fibroblast growth factor 21 (FGF21) were significantly decreased (Figure B). In patients with cholesterol crystals, the protein expressions of FOLR3, Secreted frizzled-related protein 1 (SFRP1), and Anterior gradient protein 2 homolog (AGR2) were significantly decreased (Figure C). In patients with microvessels, the expression of FOLR3 was significantly decreased (Figure D).
Conclusion
These proteins might be new biomarkers in patients with coronary high-risk plaques.
Abstract
Background
Clinical hypertension is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. IL-1 receptor antagonist (IL-1Ra) is one of the most ...important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the Angiotensin II (AngII)-induced hypertension response. This study aimed to elucidate the effects of IL-1Ra and anti-IL-1beta antibody (01BSUR) on AngII-induced hypertension and renal inflammation.
Methods and results
To determine the contribution of IL-1Ra to AngII-induced renal inflammation, male wild-type (WT) and IL-1Ra-deficient (IL-1Ra−/−) mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. We checked blood pressure, histological change, and several mRNA expressions 14 days after infusion. Fourteen days after infusion, systolic blood pressure (197±5 vs 169±9 mmHg, p<0.05) in IL-1Ra−/− mice significantly increased compared with WT mice. Furthermore, on day 14 of AngII infusion, plasma IL-6 was 5.9-fold higher in IL-1Ra−/− versus WT mice (p<0.001); renal preproendothelin-1 mRNA expression was also significantly higher in IL-1Ra−/− mice (p<0.05). To examine renal function, we analyzed 24-hour urinary protein excretion and serum levels of blood urea nitrogen, creatinine, and uric acid in IL-1Ra−/− and WT mice. On day 14 of Ang II infusion, all levels increased significantly in IL-1Ra−/− mice compared with WT mice, suggesting that IL-1Ra deficiency reduced renal function following Ang II infusion. In addition, renal histology revealed that glomerular injury (Figure upper panels: PAS staining) and tubulointerstitial fibrosis (Figure lower panels: Elastica Masson staining) increased significantly in Ang II-infused IL-1Ra−/− versus Ang II-infused WT mice. Finally, we administrated 01BSUR to both IL-1Ra−/− and WT mice, and 01BSUR treatment decreased AngII-induced hypertension (162±17 vs 204±6 mmHg, p<0.05) and renal damage (glomerular injury and fibrosis of the tubulointerstitial area) in both IL-1Ra−/− and WT mice compared with IgG2a treatment. These findings suggest that 01BSUR suppresses Ang II-induced inflammation and renal injury.
Conclusions
Inhibition of interleukin-1 by both endogenous IL-1Ra and exogenous 01BSUR decreased AngII-induced hypertension and renal damage in mice, suggesting suppression of IL-1 may provide an additional strategy to protect against renal damage in hypertensive patients.
Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI
PHENIX reports differential cross sections of μμ pairs from semileptonic heavy-flavor decays and the Drell-Yan production mechanism measured in p+p collisions at s=200 GeV at forward and backward ...rapidity (1.2<|η|<2.2). The μμ pairs from cc¯, bb¯, and Drell-Yan are separated using a template fit to unlike- and like-sign muon pair spectra in mass and pT. The azimuthal opening angle correlation between the muons from cc¯ and bb¯ decays and the pair-pT distributions are compared to distributions generated using PYTHIA and POWHEG models, which both include next-to-leading order processes. The measured distributions for pairs from cc¯ are consistent with PYTHIA calculations. The cc¯ data present narrower azimuthal correlations and softer pT distributions compared to distributions generated from POWHEG. The bb¯ data are well described by both models. The extrapolated total cross section for bottom production is 3.75±0.24(stat)±0.500.35(syst)±0.45(global) μb, which is consistent with previous measurements at the Relativistic Heavy Ion Collider in the same system at the same collision energy and is approximately a factor of 2 higher than the central value calculated with theoretical models. The measured Drell-Yan cross section is in good agreement with next-to-leading-order quantum-chromodynamics calculations.
We report the first measurement of rapidity-odd directed flow (v1) for D0 and D0¯ mesons at midrapidity (|y|<0.8) in Au+Au collisions at sNN=200 GeV using the STAR detector at the Relativistic Heavy ...Ion Collider. In 10–80% Au+Au collisions, the slope of the v1 rapidity dependence (dv1/dy), averaged over D0 and D0¯ mesons, is −0.080±0.017(stat)±0.016(syst) for transverse momentum pT above 1.5 GeV/c. The absolute value of D0 meson dv1/dy is about 25 times larger than that for charged kaons, with 3.4σ significance. These data give a unique insight into the initial tilt of the produced matter, and offer constraints on the geometric and transport parameters of the hot QCD medium created in relativistic heavy-ion collisions.
Here, we report the energy dependence of mid-rapidity (anti-)deuteron production in Au+Au collisions at $ \sqrt{s_{NN}}$ = 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV, measured by the STAR ...experiment at RHIC. The yield of deuterons is found to be well described by the thermal model. The collision energy, centrality, and transverse momentum dependence of the coalescence parameter B2 are discussed. We find that the values of B2 for antideuterons are systematically lower than those for deuterons, indicating that the correlation volume of antibaryons is larger than that of baryons at $ \sqrt{s_{NN}}$ from 19.6 to 39 GeV. In addition, values of B2 are found to vary with collision energy and show a broad minimum around $ \sqrt{s_{NN}}$ = 20 to 40 GeV, which might imply a change of the equation of state of the medium in these collisions.
We report on the first measurement of the charmed baryon Λc± production at midrapidity (|y|<1) in Au+Au collisions at sNN=200 GeV collected by the STAR experiment at the Relativistic Heavy Ion ...Collider. The Λc/D0 denoting (Λc++Λc−)/(D0+D¯0) yield ratio is measured to be 1.08±0.16 (stat)±0.26 (sys) in the 0%–20% most central Au+Au collisions for the transverse momentum (pT) range 3<pT<6 GeV/c. This is significantly larger than the pythia model calculations for p+p collisions. The measured Λc/D0 ratio, as a function of pT and collision centrality, is comparable to the baryon-to-meson ratios for light and strange hadrons in Au+Au collisions. Model calculations including coalescence hadronization for charmed baryon and meson formation reproduce the features of our measured Λc/D0 ratio.
We present the measurement of the transverse single-spin asymmetry of weak boson production in transversely polarized proton-proton collisions at s=500 GeV by the STAR experiment at RHIC. The ...measured observable is sensitive to the Sivers function, one of the transverse-momentum-dependent parton distribution functions, which is predicted to have the opposite sign in proton-proton collisions from that observed in deep inelastic lepton-proton scattering. These data provide the first experimental investigation of the nonuniversality of the Sivers function, fundamental to our understanding of QCD.
We report the first measurement of the inclusive jet and the dijet longitudinal double-spin asymmetries, ALL, at midrapidity in polarized pp collisions at a center-of-mass energy s=510 GeV. The ...inclusive jet ALL measurement is sensitive to the gluon helicity distribution down to a gluon momentum fraction of x≈0.015, while the dijet measurements, separated into four jet-pair topologies, provide constraints on the x dependence of the gluon polarization. Both results are consistent with previous measurements made at s=200 GeV in the overlapping kinematic region, x>0.05, and show good agreement with predictions from recent next-to-leading order global analyses.
Abstract
Background
One of the limitations of metallic stents including contemporary drug eluting stents lies in the permanent existence of metallic materials within the coronary arteries, which may ...lead to neoatherosclerosis and a long-term use of dual antiplatelet therapy. Some reports have recently suggested the efficacy and safety of non-stent strategy with drug-coated balloon (DCB) angioplasty in combination with debulking devices for de novo lesions. However, little is known about the potential risk of restenosis after percutaneous coronary intervention (PCI) with DCB.
Purpose
We sought to assess the predictive factors of restenosis by optical coherence tomography (OCT) after PCI with DCB instead of metallic stents.
Methods
We retrospectively investigated 49 de novo lesions in 38 patients treated by DCB without stent implantation in whom OCT was performed immediately after PCI and follow-up angiography was performed at median of 5.6 (3.7–6.9) months. OCT findings after PCI and the incidence of restenosis at follow-up angiography were evaluated. By means of OCT images, medial coronary dissection was defined as a dissection which reached the medial layer of the vessel, and major dissection was defined as a dissection with more than 60 degrees of the circumference of the vessel or more than 3mm in length. Restenosis was defined as more than 50% diameter stenosis evaluated by Quantitative Coronary Angiography.
Results
Restenosis was observed in 13 of 49 lesions (27%). In univariate logistic regression analysis, major dissection and medial dissection at the final OCT were associated with restenosis (Odds ratio OR 10.0; 95% confidence interval CI 2.5–52.6; p<0.01 and OR 5.8; 95% CI 1.5–25.1; p=0.01, respectively). Lesion preparation prior to DCB were performed with rotational atherectomy (n=9), orbital atherectomy (n=2), directional atherectomy (n=4), excimer laser angioplasty (n=17), scoring balloon angioplasty (n=13), or balloon angioplasty (n=4). OCT-defined major dissection remained a significant predictor for restenosis independent of debulking devices used for the preparation (OR 8.1; 95% CI 1.2–70.2; p=0.03).
Conclusions
Major dissection was associated with restenosis after non-stenting PCI with DCB. Stent implantation should be considered in cases of OCT-defined major dissection.
Acknowledgement/Funding
None
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