Background Percutaneous coronary intervention (PCI) had become the major therapeutic procedure for coronary artery disease (CAD), but the high rate of in-stent restenosis (ISR) still remained an unsolved clinica...Background Percutaneous coronary intervention (PCI) had become the major therapeutic procedure for coronary artery disease (CAD), but the high rate of in-stent restenosis (ISR) still remained an unsolved clinical problem in clinical practice. Increasing evidences suggested that diabetes mellitus (DM) was a major risk factor for ISR, but the risk predictors of ISR in CAD patients with DM had not been well characterized. The aim of this study was to investigate the clinical and angiographic characteristic predictors significantly associated with the occurrence of ISR in diabetic patients following coronary stenting with drug-eluting stent (DES). Methods A total of 920 patients with diabetes who diagnosed CAD and underwent coronary DES implantation at Beijing Anzhen Hospital in China were consecutively enrolled from January 2012 to December 2012. Of these, 440 patients underwent the second angiography within ≥ 6 months due to the progression of treated target lesions. Finally, 368 of these patients who met the inclusion and exclusion criteria were followed up by angiography after baseline PCI. According to whether ISR was detected at follow-up angiography, patients were divided into the ISR group (n = 74) and the non-ISR group (n = 294). The independent predictors of ISR in patients with DM were explored by multivariate Cox's proportional hazards regression models. Results A total of 368 patients (260 women and 108 men) with a mean ages of 58.71 ± 10.25 years were finally enrolled in this study. Of these, ISR occurred in 74/368 diabetic patients (20.11%) by follow-up angiography. Univariate analysis showed that most baseline characteristics of the ISR and non-ISR group were similar. Patients in the ISR group had significantly higher serum very low density lipoprotein cholesterol (VLDL-C), triglyceride (TG) and uric acid (UA) levels, more numbers of target vessel lesions, higher prevalence of multi-vessel disease, higher SYNTAX score, higher rate of previous but lower rate of drinking compared with patients in the non-ISR group. The independent predictors of ISR in patients with DM after DES implantation included VLDL-C (HR = 1.85, 95% CI: 1.24-2.77, P = 0.002), UA (per 50 μmol/L increments, HR = 1.19, 95% CI: 1.05 1.34, P = 0.006), SYNTAX score (per 5 increments, HR = 1.34, 95% CI: 1.03-1.74, P = 0.031) and the history ofPCI (HR = 3.43, 95% CI: 1.57-7.80, P = 0.003) by the multivariate Cox's proportional hazards regression analysis. Conclusions The increased serum VLDL-C and UA level, higher SYNTAX score and the history of previous PCI were independent predictors of ISR in patients with DM after coronary DES implantation. It provided new evidence for physi- cians to take measures to lower the risk oflSR for the better management of diabetic patients after PCI.展开更多
Objective To investigate the prevalence of abnormity of blood lipid and associated factors in healthy population in Beijing. Methods Totally, 38 462 individuals who received health examination were enrolled in our stu...Objective To investigate the prevalence of abnormity of blood lipid and associated factors in healthy population in Beijing. Methods Totally, 38 462 individuals who received health examination were enrolled in our study. We divided them into eight groups according to their ages. The levels of serum total cholesterol, triglyceride, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were tested, and the relationship of blood lipid abnormity with body mass index (BMI) and fasting blood glucose was analyzed. Results The incidences of hypercholesterolemia, hyperglyceridemia, low high-density lipoprotein cholesterolemia, and hyper low-density lipoprotein cholesterolemia presented increasing trend in this population. The incidence rate of abnormity of blood lipid in health examination population increased with BMI increase. The incidence of abnormity of blood lipid in overweight and obesity population was significantly higher than that in low weight and normal weight populations (P<0.05). Meanwhile, the trend of abnormal blood lipid incidence coincided with that of abnormal fasting blood glucose. Conclusions The prevalence of overweight, obesity, and abnormity of blood lipid in Beijing presents increasing trend. The incidence of abnormity of blood lipid increases with BMI increase, in coincidence with that of fasting blood glucose.展开更多
Objective To investigate the molecular mechanism of atherosclerosis that related to age. Methods Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kap...Objective To investigate the molecular mechanism of atherosclerosis that related to age. Methods Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kappa B (NF-κB) and expression of platelet-derived growth factor B (PDGF-B) in smooth muscle cells (SMCs) co-cultured with low density lipoprotein (LDL), oxidized LDL (ox-LDL), and ox-LDL+high density lipoprotein (HDL) originated from rats of 2 and 10 months old respectively. Fat stain was used to identify the lipid intake in SMCs. Results The optimal stimulation time of ox-LDL to SMCs was 12 hours. NF-κB intensity increased in most nuclei of SMCs that originated from rats of either 2 or 10 months old co-cultured with ox-LDL. The intensity of NF-κB and the amount of intracellular lipid taken in SMCs were more obvious in cells from 10-month-old rats than from the younger ones. Change of PDGF-B expression in SMCs was not remarkable in each group of rats. Conclusions The 10-month-old rats are more susceptive to ox-LDL than 2-month-old rats in activating nuclear transloca- tion of NF-κB. Maybe this is one of the important reasons contributing to the difference between the older and younger rats on the initiation and development of atherosclerosis lesion. Expression of PDGF-B is not associated with the activity of nuclear translocation of NF-κB.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
Objective To investigate the effects of insulin-like growth factor-1 (IGF-1) and oxidized low density lipoprotein (oxLDL) on expression ofphosphatase PHLPP 1 in vascular smooth muscle cells (VSMCs). Methods Rabb...Objective To investigate the effects of insulin-like growth factor-1 (IGF-1) and oxidized low density lipoprotein (oxLDL) on expression ofphosphatase PHLPP 1 in vascular smooth muscle cells (VSMCs). Methods Rabbit aortic VSMCs were cultured. VSMCs proliferation ability was determined by measuring cell number and mitochondrial dehydrogenase (MD) activity with MTT assay. Western blot was used to detect the protein expression ofphosphatase PHLPP1. Results IGF-1 (100ug/L) increased cell number and MD activity to 3.02 and 3.59 times of that in control group, oxLDL(501xg/ml) elevated the above two parameters to 2.03 and 2.91 times respectively. Western blot showed that IGF-1 and oxLDL inhibited the expression of PHLPPI to 39.27% and 40.26% of the control group (P〈0.01 ). Conclusion IGF- 1 and oxLDL may enhance the proliferation of VSMCs by decreasing the expression ofphosphatase PHLPP 1.展开更多
Selenium is a crucial trace element that contributes to physiological processes in the body as selenoproteins.Selenoproteins serve as an integral role in the body in controlling the redox state of cells and protecting...Selenium is a crucial trace element that contributes to physiological processes in the body as selenoproteins.Selenoproteins serve as an integral role in the body in controlling the redox state of cells and protecting against damage induced by oxidative stress.This study aimed to investigate the effects and possible mechanism of selenium on selenoproteins expression in EA.hy926 cells induced by oxidized low density lipoprotein(oxLDL).The impact of selenium on the viability of EA.hy926 cells was detected by the methylthiazolyldiphenyltetrazolium bromide(MTT)method,and intracellular reactive oxygen species(ROS)level and mitochondrial membrane potential were assessed by fluorescent probe DCFH-DA and JC-1,respectively.RNA-seq,quantitative real-time polymerase chain reaction(qPCR),and Western blot were used to investigate the selenoprotein expression.Selenoprotein mRNA translation efficiency was analyzed by ribosome profiling(Ribo-Seq)coupled with transcriptomics.Our data showed that selenium supplementation(0.5μmol/L)significantly decreased ROS production,increased mitochondrial inner membrane potential and increased the proliferative activity of EA.hy926 cells induced by oxLDL.Moreover,The protective effects of selenium against oxLDL-induced EA.hy926 cell injury were associated with the upregulation of the expressions of selenoproteins glutathione peroxidase 1(GPX1),glutathione peroxidase 4(GPX4),and thioredoxin reductase 1(TXNRD1).Furthermore,the expressions of selenoproteins GPX1 and GPX4 were hierarchically controlled,but the expressions of selenoproteins TXNRD1 were mainly regulated by oxLDL.Finally,Ribo-Seq coupled with transcriptomics results demonstrated that the expressions of selenoproteins GPX1,GPX4,and TXNRD1 were regulated at the translation process level.These findings suggested that selenium could have preventive effects in oxLDL induced EA.hy926 cell injury by regulating the selenoprotein expression,and the selenoproteins expressions at the translation level in vascular endothelial cells need further study.展开更多
文摘Background Percutaneous coronary intervention (PCI) had become the major therapeutic procedure for coronary artery disease (CAD), but the high rate of in-stent restenosis (ISR) still remained an unsolved clinical problem in clinical practice. Increasing evidences suggested that diabetes mellitus (DM) was a major risk factor for ISR, but the risk predictors of ISR in CAD patients with DM had not been well characterized. The aim of this study was to investigate the clinical and angiographic characteristic predictors significantly associated with the occurrence of ISR in diabetic patients following coronary stenting with drug-eluting stent (DES). Methods A total of 920 patients with diabetes who diagnosed CAD and underwent coronary DES implantation at Beijing Anzhen Hospital in China were consecutively enrolled from January 2012 to December 2012. Of these, 440 patients underwent the second angiography within ≥ 6 months due to the progression of treated target lesions. Finally, 368 of these patients who met the inclusion and exclusion criteria were followed up by angiography after baseline PCI. According to whether ISR was detected at follow-up angiography, patients were divided into the ISR group (n = 74) and the non-ISR group (n = 294). The independent predictors of ISR in patients with DM were explored by multivariate Cox's proportional hazards regression models. Results A total of 368 patients (260 women and 108 men) with a mean ages of 58.71 ± 10.25 years were finally enrolled in this study. Of these, ISR occurred in 74/368 diabetic patients (20.11%) by follow-up angiography. Univariate analysis showed that most baseline characteristics of the ISR and non-ISR group were similar. Patients in the ISR group had significantly higher serum very low density lipoprotein cholesterol (VLDL-C), triglyceride (TG) and uric acid (UA) levels, more numbers of target vessel lesions, higher prevalence of multi-vessel disease, higher SYNTAX score, higher rate of previous but lower rate of drinking compared with patients in the non-ISR group. The independent predictors of ISR in patients with DM after DES implantation included VLDL-C (HR = 1.85, 95% CI: 1.24-2.77, P = 0.002), UA (per 50 μmol/L increments, HR = 1.19, 95% CI: 1.05 1.34, P = 0.006), SYNTAX score (per 5 increments, HR = 1.34, 95% CI: 1.03-1.74, P = 0.031) and the history ofPCI (HR = 3.43, 95% CI: 1.57-7.80, P = 0.003) by the multivariate Cox's proportional hazards regression analysis. Conclusions The increased serum VLDL-C and UA level, higher SYNTAX score and the history of previous PCI were independent predictors of ISR in patients with DM after coronary DES implantation. It provided new evidence for physi- cians to take measures to lower the risk oflSR for the better management of diabetic patients after PCI.
基金Sponsored by grant of Young Scientist of PUMC Hospital (200577A)
文摘Objective To investigate the prevalence of abnormity of blood lipid and associated factors in healthy population in Beijing. Methods Totally, 38 462 individuals who received health examination were enrolled in our study. We divided them into eight groups according to their ages. The levels of serum total cholesterol, triglyceride, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were tested, and the relationship of blood lipid abnormity with body mass index (BMI) and fasting blood glucose was analyzed. Results The incidences of hypercholesterolemia, hyperglyceridemia, low high-density lipoprotein cholesterolemia, and hyper low-density lipoprotein cholesterolemia presented increasing trend in this population. The incidence rate of abnormity of blood lipid in health examination population increased with BMI increase. The incidence of abnormity of blood lipid in overweight and obesity population was significantly higher than that in low weight and normal weight populations (P<0.05). Meanwhile, the trend of abnormal blood lipid incidence coincided with that of abnormal fasting blood glucose. Conclusions The prevalence of overweight, obesity, and abnormity of blood lipid in Beijing presents increasing trend. The incidence of abnormity of blood lipid increases with BMI increase, in coincidence with that of fasting blood glucose.
文摘Objective To investigate the molecular mechanism of atherosclerosis that related to age. Methods Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kappa B (NF-κB) and expression of platelet-derived growth factor B (PDGF-B) in smooth muscle cells (SMCs) co-cultured with low density lipoprotein (LDL), oxidized LDL (ox-LDL), and ox-LDL+high density lipoprotein (HDL) originated from rats of 2 and 10 months old respectively. Fat stain was used to identify the lipid intake in SMCs. Results The optimal stimulation time of ox-LDL to SMCs was 12 hours. NF-κB intensity increased in most nuclei of SMCs that originated from rats of either 2 or 10 months old co-cultured with ox-LDL. The intensity of NF-κB and the amount of intracellular lipid taken in SMCs were more obvious in cells from 10-month-old rats than from the younger ones. Change of PDGF-B expression in SMCs was not remarkable in each group of rats. Conclusions The 10-month-old rats are more susceptive to ox-LDL than 2-month-old rats in activating nuclear transloca- tion of NF-κB. Maybe this is one of the important reasons contributing to the difference between the older and younger rats on the initiation and development of atherosclerosis lesion. Expression of PDGF-B is not associated with the activity of nuclear translocation of NF-κB.
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Objective To investigate the effects of insulin-like growth factor-1 (IGF-1) and oxidized low density lipoprotein (oxLDL) on expression ofphosphatase PHLPP 1 in vascular smooth muscle cells (VSMCs). Methods Rabbit aortic VSMCs were cultured. VSMCs proliferation ability was determined by measuring cell number and mitochondrial dehydrogenase (MD) activity with MTT assay. Western blot was used to detect the protein expression ofphosphatase PHLPP1. Results IGF-1 (100ug/L) increased cell number and MD activity to 3.02 and 3.59 times of that in control group, oxLDL(501xg/ml) elevated the above two parameters to 2.03 and 2.91 times respectively. Western blot showed that IGF-1 and oxLDL inhibited the expression of PHLPPI to 39.27% and 40.26% of the control group (P〈0.01 ). Conclusion IGF- 1 and oxLDL may enhance the proliferation of VSMCs by decreasing the expression ofphosphatase PHLPP 1.
基金supported by grants from the National Natural Science Foundation of China(NSFC,81960588)the Ningxia Natural Science Foundation(2020AAC03146)support from the Ningxia Medical University。
文摘Selenium is a crucial trace element that contributes to physiological processes in the body as selenoproteins.Selenoproteins serve as an integral role in the body in controlling the redox state of cells and protecting against damage induced by oxidative stress.This study aimed to investigate the effects and possible mechanism of selenium on selenoproteins expression in EA.hy926 cells induced by oxidized low density lipoprotein(oxLDL).The impact of selenium on the viability of EA.hy926 cells was detected by the methylthiazolyldiphenyltetrazolium bromide(MTT)method,and intracellular reactive oxygen species(ROS)level and mitochondrial membrane potential were assessed by fluorescent probe DCFH-DA and JC-1,respectively.RNA-seq,quantitative real-time polymerase chain reaction(qPCR),and Western blot were used to investigate the selenoprotein expression.Selenoprotein mRNA translation efficiency was analyzed by ribosome profiling(Ribo-Seq)coupled with transcriptomics.Our data showed that selenium supplementation(0.5μmol/L)significantly decreased ROS production,increased mitochondrial inner membrane potential and increased the proliferative activity of EA.hy926 cells induced by oxLDL.Moreover,The protective effects of selenium against oxLDL-induced EA.hy926 cell injury were associated with the upregulation of the expressions of selenoproteins glutathione peroxidase 1(GPX1),glutathione peroxidase 4(GPX4),and thioredoxin reductase 1(TXNRD1).Furthermore,the expressions of selenoproteins GPX1 and GPX4 were hierarchically controlled,but the expressions of selenoproteins TXNRD1 were mainly regulated by oxLDL.Finally,Ribo-Seq coupled with transcriptomics results demonstrated that the expressions of selenoproteins GPX1,GPX4,and TXNRD1 were regulated at the translation process level.These findings suggested that selenium could have preventive effects in oxLDL induced EA.hy926 cell injury by regulating the selenoprotein expression,and the selenoproteins expressions at the translation level in vascular endothelial cells need further study.