Elevated serum miR-133a predicts patients at risk of periprocedural myocardial injury after elective percutaneous coronary intervention

Background: Periprocedural myocardial injury (PMI) is a frequent complication of percutaneous coronary intervention (PCI) associated with poor prognosis. However, no effective method has been found to identify patients at risk of PMI before the procedure. MicroRNA-133a (miR-133a) has been reported as a novel biomarker in various cardiovascular diseases. Herein, it was sought to determine whether circulating miR-133a could predict PMI before the procedure. Methods: Eighty patients with negative preoperative values of cardiac troponin T (cTnT) receiving elective PCI for stable coronary artery disease (CAD) were recruited. Venous serum samples were collected on admission and within 16–24 hours post-PCI for miRNA measurements. PMI was defined as a cTnT value above the 99% upper reference limit (URL) after the procedure. The association between miR-133a and PMI was further assessed. Results: Periprocedural myocardial injury occurred in 48 patients. The circulating level of miR-133a was significantly higher in patients with PMI before and after the procedure (both p < 0.001). Receiver operating characteristic curve analysis of the preoperative miR-133a level revealed an area under the curve (AUC) of 0.891, with a sensitivity of 93.8% and a specificity of 71.9% to predict PMI. Additionally, a decrease was found in fibroblast growth factor receptor 1 (FGFR1) in parallel with an increase in miR-133a levels in patients with PMI. Conclusions: This study demonstrates for the first time that serum miR-133a can be used as a novel biomarker for early identification of stable CAD patients at risk of PMI undergoing elective PCI. The miR-133a-FGFR1 axis may be involved in the pathogenesis of PMI

Changes of dendritic cells and fractalkine in type 2 diabetic patients with unstable angina pectoris: a preliminary report

<p>Abstract</p> <p>Background</p> <p>It has been shown that dendritic cells (DCs) and fractalkine play a role in accelerating progression of the inflamed atherosclerotic lesions and plaque rupture. We evaluated the numbers and functional changes of DCs and its subsets in human type 2 diabetes with or without unstable angina pectoris (UAP).</p> <p>Methods</p> <p>The study population consisted of 39 diabetic patients (DM:18 without CAD; DM + UAP: 21 with UAP), 18 non-diabetic UAP patients (UAP), and 15 healthy control (Normal). Peripheral blood DCs and its subsets were measured by three color flow cytometry. Serum levels of fractalkine, IL-12, and IFN-α were also measured. The functional status of the monocyte-derived DCs was analyzed by flow cytometry and allogeneic mixed T lymphocytes reaction.</p> <p>Results</p> <p>The percent and absolute numbers of DCs and mDC within the total leukocyte population was similar for Normal and DM, while significantly lower in DM + UAP. pDC numbers were not significantly altered. Serum fractalkine in DM + UAP was highest among the four groups (<it>p </it>= 0.04 vs. UAP, <it>p </it>= 0.0003 vs. DM, <it>p </it>< 0.0001 vs. Normal). Circulating mDC inversely correlated with serum fractalkine (r = -0.268, <it>p </it>= 0.01) level. Compared with DM and UAP, the costimulatory molecules CD86 and proliferation of T cells stimulated by DCs were significantly increased in DM + UAP group.</p> <p>Conclusions</p> <p>Our study suggested that increases in the fractalkine level and the number and functional changes of blood DCs might contribute to diabetic coronary atherosclerosis and plaque destabilization.</p

Proteomics Analysis of Myocardial Tissues in a Mouse Model of Coronary Microembolization

Coronary microembolization (CME) is an important clinical problem, and it is related to poor outcome. The specific molecular mechanisms of CME are not fully understood. In the present study, we established a mice model of CME. Isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technologies identified 249 differentially expressed proteins in the myocardial tissues of CME mice as compared with sham-operated mice. Bioinformatics analysis demonstrated that these differentially expressed proteins were enriched in several energy metabolism or cytoskeleton organization related processes or pathways. Quantitative PCR and Western blotting validation experiments revealed that succinate dehydrogenase (SDHA and SDHB) were upregulated, Rho GDP dissociation inhibitor α (RhoGDIα) and Filamin-A (FLNA) were downregulated significantly in CME mice. These findings indicated that the alternations of the cytoskeleton and energy metabolism pathways play important roles in the pathogenesis of CME, future studies are warranted to verify if targeting these molecules might be useful to alleviate CME injury or not

Clinical outcomes and risk factors of coronary artery aneurysms after successful percutaneous coronary intervention and drug-eluting stent implantation for chronic total occlusions

AbstractObjectiveThe study aimed to analyze the risk factors and long-term outcomes associated with coronary artery aneurysms (CAAs) after successful percutaneous coronary intervention (PCI) and drug-eluting stent (DES) implantation in patients with CTOs.BackgroundThere are sporadic data available on post-procedure CAAs after transcatheter revascularization for CTOs.Methods and resultsA total of 141 patients with 149 CTOs who underwent successful CTO-PCI and DES implantation with angiographic follow-up from 2004 to 2010 were included. Patients were divided into CAA group and non-CAA group according to the presence of CAAs in the follow-up angiography. The independent predictors and major adverse cardiac events (MACEs) including cardiac death, myocardial infarction (MI) and target-vessel revascularization (TVR) were compared between two groups. The incidence of CAAs was 11.4% (17/149) after index procedure. Multivariate analysis showed that age (OR: 0.925, CI 0.873–0.980, P = 0.008), ostial occlusion (OR: 6.715, CI 1.473–30.610, P = 0.014), the parallel wire technique (OR: 6.167, CI 1.709–22.259, P = 0.005) and DES length (OR: 1.030, CI 1.002–1.058, P = 0.036) were the independent predictors of CAAs after successful CTO-PCI and DES implantation. MACEs were similar between two groups (adjusted hazard ratio 0.670; 95% CI 0.160–2.808; P = 0.584) during the 5-year follow-up.ConclusionsThe independent predictors of CAAs after successful CTO-PCI and DES implantation are age, ostial occlusion, the parallel wire technique and DES length. CAAs after index procedure are not frequently associated with adverse clinical events under dual antiplatelet therapy. Further large clinical studies are warranted to explore the clinical implications of patients with this distinct new entity

High Density Lipoprotein Protects Mesenchymal Stem Cells from Oxidative Stress-Induced Apoptosis via Activation of the PI3K/Akt Pathway and Suppression of Reactive Oxygen Species

The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS