Qun Lu

Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 µg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

ApoB/apoA1 is an effective predictor of coronary heart disease risk in overweight and obesity

We investigated the relationship of apoB/apoA1 ratio and coronary heart disease (CHD) in persons who were overweight or obese. The subjects were divided by the body mass indexes (BMI) into the normal weight group (n=397, BMI<24 kg/m2) and the overweight group (n=400, BMI>24 kg/m2). Our results showed that the over-weight group had higher blood pressure [(130.15±19.01) mmHg vs (123.66±18.70) mmHg] and higher levels of blood sugar [(7.09±2.89) mmol/L vs (6.21±2.59) mmol/L], triglyceride [(1.93±1.19) mmol/L vs (1.44±0.85) mmol/L], total cholesterol [(4.26±1.06) mmol/L vs (4.09±0.99) mmol/L], low-density lipoprotein cholesterol (LDL-C) [(2.56±0.75) mmol/L vs (2.39±0.72) mmol/L], and apoB [(0.83±0.27) mg/L vs (0.78±0.23) mg/L], and a higher apoB/apoA1 ratio (0.83±0.27 vs 0.75±0.25) and lower levels high-density lipoprotein cholesterol [(1.10±0.26) mmol/L vs (1.21±0.31) mmol/L] and apoA1 [(1.04±0.20) mg/L vs (1.08±0.22) mg/L] than those of the normal weight group (all P < 0.05). The prevalence of CHD in the over-weight group in the lowest LDL quartile was almost twice greater than that of the highest apoB/apoA1 quartile, compared with the subjects in the lowest apoB/apoA1 quartile. The higher apoB/apoA1 quartile was in agreement with the higher prevalence of CHD. In the overweight and obesity group, the area under ROC curve (AUC) was the highest for apoB/apoA1 (0.655). The cut-off point of apoB/apoA1 for optimal sensitivity and specificity was at 0.80, with a sensitivity of 57.19% and a specificity of 71.72%. In conclusion, apoB and apoA1 were simple clinical indicators, and the apoB/apoA1 ratio was closely related with CHD in overweight and obese patients. The apoB/apoA1 ratio may provide some useful information in the differential diagnosis.

Effect of MTHFR Gene Polymorphism Impact on Atherosclerosis via Genome-Wide Methylation

Background Atherosclerosis seriously threats human health. Homocysteine is an independent risk factor closely related to DNA methylation. MTHFR C667T loci polymorphism is closely associated with homocysteine level. This study aimed to investigate the relationship among MTHFR C667T loci polymorphism, genome-wide methylation, and atherosclerosis. Material/Methods Blood sample was collected from 105 patients with coronary atherosclerosis and 105 healthy controls. Pyrosequencing methylation was used to detect LINE-1 methylation level. Polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP) was used to test MTHFR. Results LINE-1 methylation level in the patient group was significantly lower than in the controls (t=5.007, P<0.001). MTHFR C667T genotype distribution presented marked differences in the 2 groups. TT genotype carriers had significantly increased risk of atherosclerosis (OR=3.56, P=0.009). Three different genotypes of MTHFR C667T loci showed different LINE-1 methylation level between the 2 groups (P<0.01). LINE-1 methylation level in TT and CT genotype carriers was obviously lower than in CC genotype carriers (P<0.05). Conclusions MTHFR C667T loci polymorphism may affect atherosclerosis by regulating genome methylation level.

Bisoprolol reverses down-regulation of potassium channel proteins in ventricular tissues of rabbits with heart failure ☆

Remodeling of ion channels is an important mechanism of arrhythmia induced by heart failure (HF). We investigated the expression of potassium channel encoding genes in the ventricles of rabbit established by volume-overload operation followed with pressure-overload. The reversible effect of these changes with bisoprolol was also evaluated. The HF group exhibited left ventricular enlargement, systolic dysfunction, prolongation of corrected QT interval (QTc), and increased plasma brain natriuretic peptide levels in the HF rabbits. Several potassium channel subunit encoding genes were consistently down-regulated in the HF rabbits. After bisoprolol treatment, heart function was improved significantly and QTc was shortened. Additionally, the mRNA expression of potassium channel subunit genes could be partially reversed. The down-regulated expression of potassium channel subunits Kv4.3, Kv1.4, KvLQT1, minK and Kir 2.1 may contribute to the prolongation of action potential duration in the heart of rabbits induced by volume combined with pressure overload HF. Bisoprolol could partially reverse these down-regulations and improve heart function.