ABCG1 is Expressed in an LXR-Independent Manner in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus have a high cardiovascular risk due, in part, to abnormalities of high-density lipoprotein mediated cholesterol efflux. The ATP-binding cassette A1 and G1 play a pivotal role in the regulation of cholesterol efflux. However, the regulation of these transporters in type 2 diabetes mellitus remains obscure. OBJECTIVES: This study aimed to investigate the expression of ATP-binding cassette A1 and G1 and their regulation by Liver X receptors in monocyte-derived macrophages in type 2 diabetes mellitus, and to determine whether the alteration of these transporters might affect cholesterol efflux from macrophages. METHODS: Blood was collected from type 2 diabetic patients and healthy controls. Peripheral monocytes were differentiated into macrophages. Quantitative real-time PCR, western blots, and cholesterol efflux assays were performed. The Liver X receptor and Liver X receptor element complex in the ATP-binding cassette G1 gene promoter were detected by electrophoretic mobility supershift assay. RESULTS: Macrophage ATP-binding cassette G1 expression and high density lipoproteininduced cholesterol efflux were significantly reduced in type 2 diabetic patients. However, the mRNA expression of ATP-binding cassette G1 in type 2 diabetic patients was not inhibited by Liver X receptor siRNA and the Liver X receptor- Liver X receptor element complexes remain unchanged similarly. CONCLUSION: The study suggested that the expression of ATP-binding cassette G1 and high density lipoprotein-induced cholesterol efflux in macrophages were reduced in type 2 diabetes mellitus. Impairment of cholesterol efflux and ATP-binding cassette G1 gene expression in type 2 diabetes mellitus might be regulated by a Liver X receptorindependent pathway.

Sex-related differences in left ventricular remodeling and outcome after alcohol septal ablation in hypertrophic obstructive cardiomyopathy: insights from cardiovascular magnetic resonance imaging.

BACKGROUND: Alcohol septal ablation (ASA) has been proven to reverse left ventricular (LV) remodeling in hypertrophic cardiomyopathy (HCM). However, there are no studies on the effect of sex on LV remodeling after ASA. We aimed to investigate whether sex differences affect the process of LV remodeling and outcome after ASA. METHODS: A total of 107 patients with obstructive HCM (54 men and 53 women, mean age 51 ± 8 years) were recruited. Cardiovascular magnetic resonance (CMR) was performed at baseline and 16 months after ASA. The extent of late gadolinium enhancement (LGE) was measured. RESULTS: Women had a higher indexed LV mass and smaller indexed LV end-systolic volumes than men at the time of ASA. After ASA, both men and women exhibited a regression of LV mass, and the percentage of mass regression was greater in men than women (15.3% ± 4.3% vs. 10.7% ± 1.8%, p < 0.001). In multivariable analysis, male sex, higher reduction of LV outflow tract (LVOT) gradient and lower baseline LV mass index were independently associated with greater LV mass regression after ASA. Kaplan-Meier analysis showed significantly higher cardiovascular events in women than in men (p = 0.015). Female sex [hazard ratio (HR) 3.913, p = 0.038] and LV mass preablation (HR, 1.019, p = 0.010) were independent predictors of cardiovascular outcomes. CONCLUSIONS: Males with HCM had favorable reverse remodeling with greater LV mass regression post-ASA than female patients. This favorable LV reverse remodeling might provide a mechanistic explanation for the survival advantage in men.

Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) versus alteplase (rt-PA) as fibrinolytic therapy for acute ST-segment elevation myocardial infarction (China TNK STEMI): protocol for a randomised, controlled, non-inferiority trial.

AIM: To evaluate the efficacy and safety of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) in lowering major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese acute ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, controlled non-inferiority phase IV trial with balanced randomisation (1:1) in patients with STEMI. The planned sample size is 6200 participants (or 3100 per arm). Participants with STEMI will be randomised to receive either rhTNK-tPA or alteplase (rt-PA), with stratification by research centre, age and the time from symptom onset to randomisation. All patients will receive concomitant antiplatelet and anticoagulant therapy before fibrinolytic therapy. The participants assigned to the intervention group will receive an intravenous bolus of 16 mg rhTNK-tPA, while those assigned to the control group will receive an intravenous bolus of 8 mg rt-PA followed by 42 mg infusion over 90 mins. Other medications can also be administered at the discretion of the cardiologists in charge. All participants will be followed up for the primary study endpoint, the occurrence of MACCEs within 30 days after fibrinolytic therapy, which is defined as all-cause mortality, non-fatal re-infarction, non-fatal stroke, percutaneous coronary intervention (PCI) due to thrombolysis failure, and PCI due to reocclusion. Both intention-to-treat and per-protocol analyses will be done for the primary analyses. ETHICS AND DISSEMINATION: The study procedures and informed consent form were approved by all participating hospitals. The results will be disseminated in peer review journals and academic conferences. This multicentre randomised controlled trial will provide high-quality data about the efficacy and safety of rhTNK-tPA and, once approved, its easier use should help improve the application of reperfusion therapy and hence the treatment outcomes of STEMI patients. TRIAL REGISTRATION NUMBER: NCT02835534.

Comparison of two bioelectrical impedance analysis devices with dual energy X-ray absorptiometry and magnetic resonance imaging in the estimation of body composition.

We compared a 4-limb bioelectrical impedance analysis (BIA) system, HBF 359 (Omron), and a 2-limb foot-to-foot device, BC 532 (Tanita), with the standard dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) methods for the measurement of body fat percentage (BF), skeletal muscle mass percentage (SMM, or fat-free mass [FFM] for BC 532), and visceral fat level (VF). Body composition was measured in 200 healthy volunteers (100 men and 100 women, mean age 48 years) by HBF 359 and BC 532 and by DXA and MRI. The agreement was assessed by correlation analysis and paired t-test. The correlation coefficients between BIA and DXA or MRI ranged from 0.71 to 0.89 for BF, SMM, and VF by HBF 359 and from 0.77 to 0.90 for BF, FFM, and VF by BC 532 in all subjects and in men and women separately (p < 0.001 for all). Compared with DXA, HBF 359 significantly (p < 0.001) underestimated BF by -5.8% in men and -9.6% in women. Compared with MRI, the corresponding underestimatons (negative) or overestimations (positive) by HBF 359 in men and women were, respectively, +1.9% (p = 0.02) and +1.7% (p = 0.10) for SMM, and +13.3% (p < 0.001) and -8.5% (p = 0.006), for VF. The corresponding values by BC 532 in men and women were -10.7 and -6.2% for BF, -1.4 and -2.5% for FFM, and +20.4 and -18.0% for VF. The BIA devices are accurate in the estimation of body composition, especially skeletal muscle mass or FFM.