Background Neuregulin-1 （NRG-1）, the ligand of the myocardial ErbB receptor, is a protein mediator with regulatory actions in the heart. This study investigated whether NRG-1 preconditioning has protective effects o...Background Neuregulin-1 （NRG-1）, the ligand of the myocardial ErbB receptor, is a protein mediator with regulatory actions in the heart. This study investigated whether NRG-1 preconditioning has protective effects on myocardial ischemia/reperfusion （I/R） injury and its potential mechanism.Methods We worked with an in vivo rat model with induced myocardial ischemia （45 minutes） followed by reperfusion （3 hours）. NRG-1 message was detected in the heart using RT-PCR and the protein levels of NRG-1 and ErbB4 were detected by Western blotting analysis. Infarct size was assessed using the staining agent triphenyltetrazolium chloride and cardiac function was continuously monitored. The levels of creatine kinase and lactate dehydrogenase in plasma were analyzed to assess the degree of cardiac injury. The extent of cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay and by Western blotting analysis of cleaved caspase-3. We examined the phosphorylation of Akt in the myocardium and the effect of PI3K/Akt inhibition on NRG-1-induced cardioprotection.Results Transcription and expression of NRG-1 and phosphorylation of its ErbB4 receptor were significantly upregulated in the I/R hearts. NRG-1 pretreatment reduced the infarct size following cardiac I/R in a concentration-dependent manner with an optimal concentration of 4 μg/kg in vivo. NRG-1 pretreatment with 4 μg/kg, i.v.markedly reduced the plasma creatine kinase and lactate dehydrogenase levels. Pretreatment with NRG-1 also significantly reduced the percentage of TUNEL positive myocytes and the level of cleaved caspase-3 in the I/R hearts.Pretreatment with NRG-1 significantly increased phosphorylation of Akt following I/R. Furthermore, the cardioprotective effect limiting the infarct size that was induced by NRG-1 was abolished by co-administration of the PI3K inhibitor LY294002.Conclusions The concentration of NRG-1, a new autacoid, was rapidly upregulated after myocardial I/R. NRG-1 preconditioning has cardioprotective effects against I/R injury through a PI3K/Akt-dependent mechanism in vivo.展开更多
Background The loss of cardiac myocytes is one of the mechanisms involved in acute myocardial infarction （AMI）-related heart failure. Autophagy is a common biological process in eukaryote cells. The relationship bet...Background The loss of cardiac myocytes is one of the mechanisms involved in acute myocardial infarction （AMI）-related heart failure. Autophagy is a common biological process in eukaryote cells. The relationship between cardiac myocyte loss and autophagy after AMI is still unclear. Carvedilol, a non-selective α1-and β-receptor blocker, also suppresses cardiac myocyte necrosis and apoptosis induced by ischemia. However, the association between the therapeutic effects of carvedilol and autophagy is still not well understood. The aim of the present study was to establish a rat model of AMI and observe changes in autophagy in different zones of the myocardium and the effects of carvedilol on autophagy in AMI rats. Methods The animals were randomly assigned to a sham group, an AMI group, a chloroquine intervention group and a carvedilol group. The AMI rat model was established by ligating the left anterior descending coronary artery. The hearts were harvested at 40 minutes, 2 hours, 24 hours and 2 weeks after ligation in the AMI group, at 40 minutes in the chloroquine intervention group and at 2 weeks in other groups. Presence of autophagic vacuoles （AV） in the myocytes was observed by electron microscopy. The expression of autophagy-, anti-apoptotic- and apoptotic-related proteins, MAPLC-3, Beclin-1, Bcl-xl and Bax, were detected by immunohistochemical staining and Western blotting. Results AVs were not observed in necrotic regions of the myocardium 40 minutes after ligation of the coronary artery. A large number of AVs were found in the region bordering the infarction. Compared with the infarction region and the normal region, the formation of AV was significantly increased in the region bordering the infarction （P 〈0.05）. The expression of autophagy- and anti-apoptotic-related proteins was significantly increased in the region bordering the infarction. Meanwhile, the expression of apoptotic-related proteins was significantly increased in the infarction region. In the chloroquine intervention group, a large number of initiated AVs （AVis） were found in the necrotic myocardial region. At 2 weeks after AMI, AVs were frequently observed in myocardial cells in the AMI group, the carvedilol group and the sham group, and the number of AVs was significantly increased in the carvedilol group compared with both the AMI group and the sham group （P 〈0.05）. The expression of autophagy- and anti-apoptotic-related proteins was significantly increased in the carvedilol group compared with that in the AMI group, and the positive expression located in the infarction region and the region bordering the infarction. Conclusions AMI induces the formation of AV in the myocardium. The expression of anti-apoptosis-related proteins increases in response to upregulation of autophagy. Carvedilol increases the formation of AVs and upregulates autophagy and anti-apoptosis of the cardiac myocytes after AMI.展开更多
Background Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular （LV） remodeling and heart failure （HF）. Recombinant human neuregulin-1 （rhNRG-1） improves cardiac function in mode...Background Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular （LV） remodeling and heart failure （HF）. Recombinant human neuregulin-1 （rhNRG-1） improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.展开更多
Background C-reactive protein （CRP） is a lowly expressed marker for inflammatory response. This study aimed to evaluate the prognostic value of baseline CRP levels in patients undergoing coronary revascularization i...Background C-reactive protein （CRP） is a lowly expressed marker for inflammatory response. This study aimed to evaluate the prognostic value of baseline CRP levels in patients undergoing coronary revascularization in the context of modern medical treatment. Methods This was a retrospective study in a single center. Four hundred and fourteen patients were enrolled, who underwent coronary revascularization and received adequate medication for secondary prevention of coronary heart disease. The study compared the follow-up clinical outcomes between high level CRP group （CRP 〉5 mg/L） and low level one. The median follow-up time was 551 days. Results Compared with low CRP group, the relative risk （RR） of the major adverse cardiovascular and cerebral events （MACCE） in high CRP group was 5.131 （95% CI： 1.864-14.123, P=0.002）. There were no significant differences in death myocardial infarction and stroke during the follow-up between two groups, but a higher risk of re-revascularization was found in high CRP group （RR 6.008, 95% CI： 1.667-21.665, P=0.006）. Cox regression analysis showed that only CRP level could contribute to MACCE during the follow-up. MACCE-free rate was much lower in high CRP group （Kaplan-Meier log-rank P 〈0.001）. Conclusion In the context of modern medical treatment, the baseline level of CRP is an independent predictor for long-term prognosis in patients with coronary revascularization.展开更多
Hypereosinophilic syndrome （HES） is a rare disorder that can be seen in various organ systems, but its major tissue target is the heart.＇ The most characteristic cardiovascular abnormality in HES is endomyocardial ...Hypereosinophilic syndrome （HES） is a rare disorder that can be seen in various organ systems, but its major tissue target is the heart.＇ The most characteristic cardiovascular abnormality in HES is endomyocardial fibrosis, initially described in 1936 by Loffler, who called it ＂fibroplastic parietal endocarditis with blood eosinophilia.＂ The overall prognosis of patients with Loffler endocarditis is very poor. Current treatments include anticoagulation and anti-eosinophils therapy, and surgery only has been used in selected cases.展开更多
Transcoronary ablation of septal hypertrophy （TASH） has been recommended as an option forpatients with drug-refractory hypertrophic obstructive cardiomyopathy （HOCM）. However, its outcome is varied, and some facto...Transcoronary ablation of septal hypertrophy （TASH） has been recommended as an option forpatients with drug-refractory hypertrophic obstructive cardiomyopathy （HOCM）. However, its outcome is varied, and some factors are attributed to the diversity results.1 Up to now, there is no study on the influence of the ablated myocardium＇s condition on the outcome. We retrospectively analyzed the myocardial perfusion imaging （MPI） obtained before and early after TASH in our patients to explore the relationship between the ablated myocardium＇s condition and the clinical outcome.展开更多
Background The optimal revascularization strategy in patients with heart failure with preserved ejection fraction （HFPEF） remains unclear. The aim of the present study was to compare the effects of percutaneous coro...Background The optimal revascularization strategy in patients with heart failure with preserved ejection fraction （HFPEF） remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention （PCI） and coronary artery bypass grafting （CABG） in patients with HFPEF. Methods From July 2003 through September 2005, a total of 920 patients with coronary artery disease （CAD） and HFPEF （ejection fraction 〉50%） underwent PCI （n=350） or CABG （n=570）. We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events （MACCE）, including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days. Results In-hospital mortality was significantly lower in the PCI group than in the CABG group （0.3% vs. 2.5%, adjusted P=0.016）. During follow-up, there was no significant difference in the two groups with regard to mortality rates （2.3% vs. 3.5%, adjusted P=0.423）. Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG （13.4% vs. 4.0%, adjusted P 〈0.001）, mainly due to higher rate of repeat revascularization （adjusted P 〈0.001）. Independent predictors of mortality were age, New York Heart Association （NYHA） class and chronic total occlusion. Conclusion Among patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.展开更多
基金This study was supported by the Natural Science Foundation of Beijing, China （No. 7102043） and by a Grant-in-Aid for Scientific Research from Beijing Municipal Health Bureau and the Beijing Journal of Traditional Chinese Medicine （No. QN2009-008）.
文摘Background Neuregulin-1 （NRG-1）, the ligand of the myocardial ErbB receptor, is a protein mediator with regulatory actions in the heart. This study investigated whether NRG-1 preconditioning has protective effects on myocardial ischemia/reperfusion （I/R） injury and its potential mechanism.Methods We worked with an in vivo rat model with induced myocardial ischemia （45 minutes） followed by reperfusion （3 hours）. NRG-1 message was detected in the heart using RT-PCR and the protein levels of NRG-1 and ErbB4 were detected by Western blotting analysis. Infarct size was assessed using the staining agent triphenyltetrazolium chloride and cardiac function was continuously monitored. The levels of creatine kinase and lactate dehydrogenase in plasma were analyzed to assess the degree of cardiac injury. The extent of cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay and by Western blotting analysis of cleaved caspase-3. We examined the phosphorylation of Akt in the myocardium and the effect of PI3K/Akt inhibition on NRG-1-induced cardioprotection.Results Transcription and expression of NRG-1 and phosphorylation of its ErbB4 receptor were significantly upregulated in the I/R hearts. NRG-1 pretreatment reduced the infarct size following cardiac I/R in a concentration-dependent manner with an optimal concentration of 4 μg/kg in vivo. NRG-1 pretreatment with 4 μg/kg, i.v.markedly reduced the plasma creatine kinase and lactate dehydrogenase levels. Pretreatment with NRG-1 also significantly reduced the percentage of TUNEL positive myocytes and the level of cleaved caspase-3 in the I/R hearts.Pretreatment with NRG-1 significantly increased phosphorylation of Akt following I/R. Furthermore, the cardioprotective effect limiting the infarct size that was induced by NRG-1 was abolished by co-administration of the PI3K inhibitor LY294002.Conclusions The concentration of NRG-1, a new autacoid, was rapidly upregulated after myocardial I/R. NRG-1 preconditioning has cardioprotective effects against I/R injury through a PI3K/Akt-dependent mechanism in vivo.
文摘Background The loss of cardiac myocytes is one of the mechanisms involved in acute myocardial infarction （AMI）-related heart failure. Autophagy is a common biological process in eukaryote cells. The relationship between cardiac myocyte loss and autophagy after AMI is still unclear. Carvedilol, a non-selective α1-and β-receptor blocker, also suppresses cardiac myocyte necrosis and apoptosis induced by ischemia. However, the association between the therapeutic effects of carvedilol and autophagy is still not well understood. The aim of the present study was to establish a rat model of AMI and observe changes in autophagy in different zones of the myocardium and the effects of carvedilol on autophagy in AMI rats. Methods The animals were randomly assigned to a sham group, an AMI group, a chloroquine intervention group and a carvedilol group. The AMI rat model was established by ligating the left anterior descending coronary artery. The hearts were harvested at 40 minutes, 2 hours, 24 hours and 2 weeks after ligation in the AMI group, at 40 minutes in the chloroquine intervention group and at 2 weeks in other groups. Presence of autophagic vacuoles （AV） in the myocytes was observed by electron microscopy. The expression of autophagy-, anti-apoptotic- and apoptotic-related proteins, MAPLC-3, Beclin-1, Bcl-xl and Bax, were detected by immunohistochemical staining and Western blotting. Results AVs were not observed in necrotic regions of the myocardium 40 minutes after ligation of the coronary artery. A large number of AVs were found in the region bordering the infarction. Compared with the infarction region and the normal region, the formation of AV was significantly increased in the region bordering the infarction （P 〈0.05）. The expression of autophagy- and anti-apoptotic-related proteins was significantly increased in the region bordering the infarction. Meanwhile, the expression of apoptotic-related proteins was significantly increased in the infarction region. In the chloroquine intervention group, a large number of initiated AVs （AVis） were found in the necrotic myocardial region. At 2 weeks after AMI, AVs were frequently observed in myocardial cells in the AMI group, the carvedilol group and the sham group, and the number of AVs was significantly increased in the carvedilol group compared with both the AMI group and the sham group （P 〈0.05）. The expression of autophagy- and anti-apoptotic-related proteins was significantly increased in the carvedilol group compared with that in the AMI group, and the positive expression located in the infarction region and the region bordering the infarction. Conclusions AMI induces the formation of AV in the myocardium. The expression of anti-apoptosis-related proteins increases in response to upregulation of autophagy. Carvedilol increases the formation of AVs and upregulates autophagy and anti-apoptosis of the cardiac myocytes after AMI.
文摘Background Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular （LV） remodeling and heart failure （HF）. Recombinant human neuregulin-1 （rhNRG-1） improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.
文摘Background C-reactive protein （CRP） is a lowly expressed marker for inflammatory response. This study aimed to evaluate the prognostic value of baseline CRP levels in patients undergoing coronary revascularization in the context of modern medical treatment. Methods This was a retrospective study in a single center. Four hundred and fourteen patients were enrolled, who underwent coronary revascularization and received adequate medication for secondary prevention of coronary heart disease. The study compared the follow-up clinical outcomes between high level CRP group （CRP 〉5 mg/L） and low level one. The median follow-up time was 551 days. Results Compared with low CRP group, the relative risk （RR） of the major adverse cardiovascular and cerebral events （MACCE） in high CRP group was 5.131 （95% CI： 1.864-14.123, P=0.002）. There were no significant differences in death myocardial infarction and stroke during the follow-up between two groups, but a higher risk of re-revascularization was found in high CRP group （RR 6.008, 95% CI： 1.667-21.665, P=0.006）. Cox regression analysis showed that only CRP level could contribute to MACCE during the follow-up. MACCE-free rate was much lower in high CRP group （Kaplan-Meier log-rank P 〈0.001）. Conclusion In the context of modern medical treatment, the baseline level of CRP is an independent predictor for long-term prognosis in patients with coronary revascularization.
文摘Hypereosinophilic syndrome （HES） is a rare disorder that can be seen in various organ systems, but its major tissue target is the heart.＇ The most characteristic cardiovascular abnormality in HES is endomyocardial fibrosis, initially described in 1936 by Loffler, who called it ＂fibroplastic parietal endocarditis with blood eosinophilia.＂ The overall prognosis of patients with Loffler endocarditis is very poor. Current treatments include anticoagulation and anti-eosinophils therapy, and surgery only has been used in selected cases.
文摘Transcoronary ablation of septal hypertrophy （TASH） has been recommended as an option forpatients with drug-refractory hypertrophic obstructive cardiomyopathy （HOCM）. However, its outcome is varied, and some factors are attributed to the diversity results.1 Up to now, there is no study on the influence of the ablated myocardium＇s condition on the outcome. We retrospectively analyzed the myocardial perfusion imaging （MPI） obtained before and early after TASH in our patients to explore the relationship between the ablated myocardium＇s condition and the clinical outcome.
文摘Background The optimal revascularization strategy in patients with heart failure with preserved ejection fraction （HFPEF） remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention （PCI） and coronary artery bypass grafting （CABG） in patients with HFPEF. Methods From July 2003 through September 2005, a total of 920 patients with coronary artery disease （CAD） and HFPEF （ejection fraction 〉50%） underwent PCI （n=350） or CABG （n=570）. We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events （MACCE）, including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days. Results In-hospital mortality was significantly lower in the PCI group than in the CABG group （0.3% vs. 2.5%, adjusted P=0.016）. During follow-up, there was no significant difference in the two groups with regard to mortality rates （2.3% vs. 3.5%, adjusted P=0.423）. Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG （13.4% vs. 4.0%, adjusted P 〈0.001）, mainly due to higher rate of repeat revascularization （adjusted P 〈0.001）. Independent predictors of mortality were age, New York Heart Association （NYHA） class and chronic total occlusion. Conclusion Among patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.
