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IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcζR1. In addition to mast cells, many cell types implicated in atherogenesis express FcζR1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the FcζR1 subunit FcζR1 α were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of FcζR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcζR1 activity. IgE stimulated the interaction between FcζR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcζR1 or TLR4. Furthermore, IgE activated macrophages by enhancing [[Na.sup.+]/H.sup.+] exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases., Introduction IgE is an important regulator of allergic reactions, in which it activates mast cells (MCs) by binding to its high-affinity receptor FcζR1 (1). In addition to allergic responses (2), [...]

Background: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug-drug interactions (DDIs) when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.Methods: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.Results: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John's wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C.A), species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1.Conclusion: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring. [ABSTRACT FROM AUTHOR]

Background: Cardiac implantable electronic devices (CIEDs) greatly improve survival and life quality of patients. However, there are gender differences regarding both the utilization and benefit of these devices. In this prospective CIED registry, we aim to appraise the gender differences in CIED utilization in China., Methods: Twenty centers from 14 provinces in China were included in our registry study. All patients who underwent a CIED implantation in these twenty centers between Jan 2015 and Dec 2016 were included., Results: A total of 8570 patients were enrolled in the baseline cohort, including 7203 pacemaker, 664 implantable cardiac defibrillators (ICD) implants and 703 cardiac resynchronization therapy device (CRT/D). Totally, 4117 (48.0%) CIED patients were female, and more than 59% pacemaker patients were female, but women account only one third of ICD or CRT/D implantation in this registry. There were significant differences between genders at pacemaker and ICD indications. Female was more likely received a pacemaker due to sick sinus syndrome (SSS) (63.9% vs. 51.0%, P < 0.001). Female patients receiving an ICD were more likely due to cardiac ion channel disease (29.2% vs. 4.2%, P < 0.001). The percentage of utilization of dual-chamber pacemaker in female patients was significantly higher than male (85.3% vs. 81.1%, P < 0.001). But male patients were more likely received a cardiac resynchronization therapy devices with defibrillator than female (56.5% vs. 41.9%, P = 0.001). In pacemaker patient, male was more likely to have structure heart disease (31.3% vs. 28.0%, P = 0.002). In ICD patient, male patients were more likely to have ischemic heart disease (48.2% vs. 29.2%, P < 0.001). The mean age of women at the time of CRT/D implantation was older than men ( P = 0.014). Nonischemic cardiomyopathy (70.9%) was the most common etiology in the patients who underwent the treatment of CRT/D, no matter male or female., Conclusions: In real-world setting, female do have different epidemiology, pathophysiology and clinical presentation of many cardiac rhythm disorders when compared with male, and all these factors may affect the utilization of CIED implantation. But it also possibility that cultural and socioeconomic features may play a role in this apparent discrimination.

Objective: The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC., Methods: Prospective randomized controlled trials (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies., Results: We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80, P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The percentage of patients requiring electric defibrillation counter shocks (DCSs) did not differ significantly among patients administered amiodarone (RR=0.21, 95% CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16)., Conclusions: Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.

Objective: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients., Methods: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent., Results: (1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism., Conclusion: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

Objective: To evaluate the efficacy and security of one-stop hybrid cardiac surgery for the treatment of adult patients with complex heart disease., Methods: From November 2011 to March 2012, a total of 5 patients [4 male, mean age: (58.8 ± 14.7) years] underwent one-stop hybrid approach in the hybrid operating room. Two patients suffered from multi-coronary lesions, 2 patients were diagnosed with both valvular heart disease and coronary disease, and another 1 patient had valve disease and congenital heart disease (patent ductus arteriosus). Minimally invasive cardiac surgery (coronary artery bypass grafting for the left anterior descending or valvular surgery) and percutaneous intervention were performed in an enhanced operative unit. The efficacy and security of one-stop hybrid cardiac surgery were evaluated after the procedure., Results: The one-stop hybrid procedure was successful in all patients. Left internal mammary artery grafts were unobstructed. A total of 6 non-left anterior descending coronary lesions were treated by percutaneous coronary intervention and 6 drug-eluting stents were implanted. There was no death, perioperative myocardial infarction, heart failure, prosthetic valve dysfunction, respiratory failure, stroke or repeat surgery during the procedure period. All patients remained free from angina, prosthetic valve dysfunction and patent ductus arteriosus recanalisation during the 3.2 months (rang 1 to 5 months) follow-up period., Conclusion: One-stop hybrid cardiac surgery provides a reasonable, feasible and safe alternative for treating adult patients with complex heart disease.

Objective: To investigate the effect of long-term administration of fluvastatin on improvement of ventricular remodeling of rats after myocardial infarction and its mechanism., Methods: Sprague-Dawley rats were subjected to ligation in anterior descending branch of coronary artery and treated with fluvastatin (20 mg.kg(-1) d(-1)) or distilled water for 8 weeks. Doppler echocardiography, hemodynamic study and cardiac histomorphometry were used to estimate the ventricular remodeling and cardiac function. Laser scanning confocal microscope was used to definite the distribution of superoxide anion (O(2)(*-)) and nitrogen monoxide. RT-PCR and immunohistochemistry were used to detect the expression of NOS2 and p22phox in mRNA and protein level. The level of lipid peroxidation, glutathione peroxidase, nitrogen monoxide and total cholesterol were detected too., Results: Administration of fluvastatin ameliorated left ventricular remodeling without affecting the infarct size [(40 +/- 6 vs 42 +/-5)%, P>0.05]. The level of left ventricular end-diastolic pressure [(18.24 +/-6.58 vs 10.74 +/-4.71) mmHg, P<0.05], right ventricular ameliorated relative weight [(0.92 +/-0.19 vs 0.71 +/-0.13) g/kg, P<0.05], the thickness of left ventricular posterior wall [(3.04 +/-0.28 vs 2.60 +/-0.36) mm, P<0.05] decreased after fluvastatin treatment. The left ventricular ejection fraction was not influenced, the relative lung weight and the left atrium diameter reduced [(5.79 +/-2.92 vs 3.69 +/-0.68) g/kg, (0.55 +/-0.12 vs 0.45 +/-0.04) mm, P<0.05]; the expressions of LPO in the plasma and myocardium [(8.64 +/-0.59 vs 7.71 +/-0.66) U/dl, P<0.05; (3.12 +/-0.38 vs 1.93 +/-0.40) ng/microg.pro, P<0.01] were reduced, and the overexpressed NO was inhibited [(436.87 +/-47.22 vs 313.78 +/-34.35) mg/dl, P<0.01], but the expression of GPx increased [(66.13 +/-8.31 vs 79.78 +/-2.38) mg/dl, P<0.01]. The expression of O(2)(*-) and the activity of NADPH oxidase subunit p22phox increased; NOS2 and its products NO were over-expressed too., Conclusion: Ventricular remodeling and hemodynamics are improved profoundly in MI rats treated with fluvastatin. The effect of antioxidative stress of fluvastatin might be involved in the mechanism.

Objective: To further clarify the mechanism of Ang II-induced intracellular signal transduction in vascular smooth muscle cells(VSMCs) proliferation by observing the effect of c-Src on Ang II-mediated MAPK activation and c-fos protein expressions in rat VSMCs., Methods: Aortic VSMCs from SD rats were cultured primarily and subcultured, which were transfected with anti-sense c-Src oligodeoxynucleotides(ODNs) wrapped with lipofectin to inhibit c-Src activity and protein production. Untransfected VSMCs were used as control, to observe the role of Ang II stimulation in MAPK activation and c-fos protein expression in VSMC. Protein immunoprecipitation and kinase phosphorylation were employed to measure c-Src kinase activity; MAPK kinase activity was assessed by the phosphorylation rate of the substrate MBP(Myelin Basic Protein); Western blot was used to assess the protein expression of c-Src and c-fos., Results: c-Src protein expressions in VSMC, which were transfected with different concentrations of anti-sense c-Src ODNs, were significantly decreased in a negative dose-effect manner (0.2 microm, 0.5 microm, 1.0 microm and 2.0 microm were 68.2%, 34.7%, 30.3% and 15.8% respectively compared with control). c-Src kinase activity was also obviously inhibited. Following stimulation of Ang II on VSMC transfected with anti-sense c-Src ODNs, the increase of c-Src activity was only 8.7% of control,the activity of MAPK only 1.6% compared with control, and the increase in c-fos protein expression 30.3% as control., Conclusion: Ang II can induce c-Src activation and intracellular signal transduction in VSMC which depend on c-Src activation, indicating that c-Src is a pivotal signal factor in VSMC proliferation.