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 failu...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 I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β trealanent (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 ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture 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.展开更多
Background Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics...Background Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). Methods In 127 consecutive patients with CAD but without acute coronary syndrome and who under went 64-slice CTA, MPs procoagulant activity in plasma Coy a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 〈 calcium volume (%) 〈 1), and calcified plaque (CP) group (calcium volume (%) 〉 1). Results MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P 〈 0.0001) and sLOX-1 levels (r = 0.216, P = 0.0025). Conclusions MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.展开更多
BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better...BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol(TCL), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides(TG)]and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD (r=-0.34,P〈0.001) and RA (r=-0.36,P〈0.001). Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.展开更多
基金This research was supported by the Key Program,the National Natural Science Foundation of China
文摘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 I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β trealanent (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 ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture 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.
文摘Background Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA). Methods In 127 consecutive patients with CAD but without acute coronary syndrome and who under went 64-slice CTA, MPs procoagulant activity in plasma Coy a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 〈 calcium volume (%) 〈 1), and calcified plaque (CP) group (calcium volume (%) 〉 1). Results MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P 〈 0.0001) and sLOX-1 levels (r = 0.216, P = 0.0025). Conclusions MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.
文摘BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol(TCL), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides(TG)]and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD (r=-0.34,P〈0.001) and RA (r=-0.36,P〈0.001). Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.