[Effects of allitridi capsules on endothelial function and clinical prognosis after percutaneous coronary intervention in coronary artery disease patients with diabetes mellitus].

OBJECTIVE: To explore the effects of allitridi capsules on endothelial function and clinical prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients with diabetes mellitus (DM). METHODS: A total of 120 CAD patients with DM undergoing PCI were randomly assigned to receive conventional (control, n = 60) and additional allitridi treatment (120 mg/day, n = 60) for 3 months.Serum nitric oxide (NO) and intercellular adhesion molecule 1 (ICAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA) immediately and at 3 months post-PCI. Endothelial function was assessed by endothelium dependent flow-mediated dilation (FMD). Duration of follow-up was 1 year after PCI. RESULTS: The clinical characteristics, serum NO and ICAM-1 levels and FMD at baseline were not different between two groups. At Month 3 post-PCI, serum NO level was markedly higher ((147 ± 32) vs (112 ± 24) µmol/L, P = 0.009) and serum ICAM-1 level was significantly lower ((182 ± 21) vs (232 ± 29) µmol/L, P = 0.021) in the allitridi group than in the control group.Furthermore, treatment of allitridi resulted in a significant improvement of FMD (8.2% ± 2.4% vs 6.4% ± 2.3%, P = 0.013). At Year 1 post-PCI, the incidence of major adverse cardiovascular event (MACE) was lower in the allitridi group than that in the control group (10.5% vs 17.2%, P = 0.022). CONCLUSIONS: Allitridi capsules significantly improve the clinical prognosis after PCI in CAD patients with DM. Its mechanism may lies in improved endothelial function and vascular inflammatory state.

Kruppel-like factor 2 might mediate the rapamycin-induced arterial thrombosis in vivo: implications for stent thrombosis in patients.

BACKGROUND: Stent thrombosis is one of severe complications after sirolimus-eluting stent implantation. Rapamycin (sirolimus) promotes arterial thrombosis in in vivo studies. However, the underlying molecular and transcriptional mechanisms of this adverse effect have not been thoroughly investigated. This study was designed to examine the effects of rapamycin on the expression of the gene, Kruppel-like factor 2 (KLF2), and its transcriptional targets in mice. METHODS: Mice were randomly divided into four groups: the control group (intraperitoneal injection with 2.5% of dimethyl sulfoxide (DMSO) only), rapamycin group (intraperitoneal injection with 2 mg/kg of rapamycin only), Ad-LacZ + rapamycin group (carotid arterial incubation with Ad-LacZ plus intraperitoneal injection with 2 mg/kg of rapamycin 10 days later), and Ad-KLF2 + rapamycin group (carotid arterial incubation with Ad-KLF2 plus intraperitoneal injection with 2 mg/kg rapamycin 10 days later). The carotid arterial thrombosis formation was induced by FeCl3 and the time of arterial thrombosis was determined. Finally, the RNA and protein of carotid arteries were extracted for KLF2, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM) mRNA and protein analysis. RESULTS: Compared with controls, treatment with rapamycin inhibited KLF2, eNOS and TM mRNA and protein expression, and enhanced TF and PAI-1 mRNA and protein expression, and shortened time to thrombotic occlusion from (1282 ± 347) seconds to (715 ± 120) seconds (P < 0.01) in vivo. Overexpression of KLF2 strongly reversed rapamycin-induced effects on KLF2, eNOS, TM, TF and PAI-1 expression. KLF2 overexpression increased the time to thrombotic occlusion to control levels in vivo. CONCLUSIONS: Rapamycin induced an inhibition of KLF2 expression and an imbalance of anti- and pro-thrombotic gene expression, which promoted arterial thrombosis in vivo. Overexpression of KLF2 increased KLF2 expression and reversed time to thrombosis in vivo.

Influence of abnormal fasting plasma glucose on left ventricular function in older patients with acute myocardial infarction.

We assessed whether the admission fasting plasma glucose (FPG) levels were associated with all-cause mortality and left ventricular (LV) function in older patients with acute myocardial infarction (AMI). A total of 1854 consecutive patients were categorized into 4 groups: hypoglycemia, euglycemia, mild hyperglycemia, and severe hyperglycemia. The primary outcomes were in-hospital/3-year mortality and LV function. There was a near-linear relationship between FPG and Killip class. However, no significant correlation was found between FPG levels and LV ejection fraction. Both FPG levels and Killip classes were all independent significant predictors of mortality. Compared with the euglycemia group, both the hypo- and hyperglycemia groups were associated with higher in-hospital and 3-year mortality. In older patients with AMI, the FPG values had differential influences on LV function and mortality. There was a U-shaped relationship between FPG and in-hospital/3-year mortality, and a near-linear relationship between increased admission glucose levels and higher Killip classification.

[Effects of sirolimus upon endothelial thrombotic function of human umbilical vein endothelial cells].

OBJECTIVE: To explore the effects of sirolimus upon endothelial thrombotic function of human umbilical vein endothelial cells (HUVEC). METHODS: Sirolimus was added into the in vitro cultured HUVEC at the concentrations of 0 (control), 0.1, 1 and 10 ng/ml. At 2, 4, 8, 12 and 24 h post-incubation, the cells were harvested for determination of tissue factor (TF), plasminogen activator inhibitor (PAI-1), endothelial nitric oxide synthase (eNOS) and thrombomodulin (TM) expression by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The clotting functions of HUVEC were assayed by an automated coagulation analyzer. RESULTS: Sirolimus induced the expressions of TF and PAI-1 and inhibited the expressions of eNOS and TM in a concentration-dependent manner. The maximal change of mRNA expression was observed at 8 h and remained up to at least 24 h. And the most marked change of protein expression (65% reduction in eNOS expression, 52% reduction in TM, 1.7-fold increase in PAI-1 and 2.8-fold increase in TF) was at 12 h. The clotting time in sirolimus group (89 s ± 9 s) was significantly shorter than that in control group (152 s ± 17 s, P = 0.005). CONCLUSION: Sirolimus induces endothelial antithrombotic dysfunction and shortens the clotting time through an elevated expression of prothrombotic genes TF and PAI-1 and a lowered expression of antithrombotic genes eNOS and TM. It may be one of mechanisms of thrombosis after the implantation of sirolimus-eluting stents.

Effect of abnormal fasting plasma glucose level on all-cause mortality in older patients with acute myocardial infarction: results from the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS).

OBJECTIVE: To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI). PATIENTS AND METHODS: From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL [to convert to mmol/L, multiply by 0.0555]; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality. RESULTS: Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P=.36) or 3-year (24.5% vs 24.5%; P=.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex. CONCLUSION: An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.

Association between admission hypoglycaemia and in-hospital and 3-year mortality in older patients with acute myocardial infarction.

OBJECTIVE: To assess the association between fasting plasma glucose (FPG) levels on admission and mortality in older patients with acute myocardial infarction (AMI), and compare the effects of FPG levels on outcomes in the context of contemporary treatments, including drug treatment, percutaneous coronary intervention and coronary artery bypass grafting. METHODS: From April 2004 to October 2006, 1854 older (age > or =65 years) patients with AMI were enrolled in the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS) consecutively. Patients were categorised into 4 groups: hypoglycaemia group (N=443, 23.9%), FPG< or =5 mmol/l; euglycaemia group (N=812, 43.8%), FPG> or = 5.1 to< or =7.0 mmol/l (5-7 mmol/l); mild hyperglycaemia group (N=308, 16.6%), FPG> or = 7.1 to< or =9.0 mmol/l (7-9 mmol/l); and severe hyperglycaemia group (N=291, 15.7%), FPG> or =9.1 mmol/l. The primary end point was in-hospital and 3-year all-cause mortality from the day of admission. RESULTS: Compared with the euglycaemia group, hypoglycaemia or hyperglycaemia groups were all associated with higher in-hospital and 3-year all-cause mortality. There was a U-shaped relationship between admission FPG levels and short- and long-term all-cause mortality. This U-shaped relationship applied equally to subgroups in the context of contemporary treatments. CONCLUSIONS: In older patients with AMI, increased as well as decreased admission FPG levels could predict higher in-hospital and 3-year mortality. There was a striking U-shaped relationship between admission FPG levels and short- and long-term mortality. An initial admission FPG level > or = 5.1 to< or =7.0 mmol/l may be desirable because it was associated with better clinical outcomes.

Feasibility and safety of transcatheter intervention for complex patent ductus arteriosus.

We evaluated the transcatheter intervention of complex patent ductus arteriosus (PDA) in Chinese adults. Between January 2004 and April 2008, 112 adult patients (43 males, 69 females, mean age 31 +/- 19 years) underwent intervention. Coils were used for patients with small PDA, and Amplatzer duct occluders or China-made mushroom-shaped occluders were used for patients with moderate-to-large PDA. The success rate of transcatheter intervention was 93.8%, and 9 patients (8.0%) had small residual shunts. At the end of 12 months follow-up, the rate of residual shunts was 1.8%. Peak systolic pulmonary pressure decreased from 94 +/- 21 mm Hg preintervention to 58 +/- 20 mm Hg postintervention (P < .001). No severe procedure-related complications (including death, dislocation of occluders, stenosis of aorta or pulmonary artery) occurred. Some patients developed hemolysis or vascular access complications, all resolved by conservative therapy. Transcatheter intervention is an effective and safe treatment for adult PDA patients with complex anatomic or hemodynamic conditions.

[Effect of stent coated with diallyl trisulfide on endothelial structure and function after coronary injury: experiment with dogs].

OBJECTIVE: To investigate the effect of stent coated with diallyl trisulfide on endothelial structure and function after coronary injury. METHODS: Eight adult dogs were randomly divided into 2 equal groups to undergo implantation of stent coated with diallyl trisulfide (drug group) or stent not coated with diallyl trisulfide (control group) into the distal and proximal ends of the left circumflex coronary arteries respectively. Twenty-eight hours later the dogs were killed. Their coronary arteries with the stents inside were taken out and divided into 4 parts: 2 parts underwent light microscopy and scanning electron microscopy and 2 parts underwent immunohistochemistry and Western blotting to examine the levels of endothelial nitric oxide synthase (eNOS) and nitrogen monoxide (NO). RESULTS: The thickness of intima of the control group was 0.35 mm +/- 0.11 mm, significantly greater than that of the drug group (0.12 mm +/- 0.05 mm, P < 0.01); the area of intima of the control group was 1.81 mm(2) +/- 0.36 mm(2), significantly greater than that of the drug group (1.17 mm(2) +/- 0.25 mm(2), P < 0.05). The endothelial cells in the intima of the drug group were tighter and more orderly than those of the control group. Immunohistochemistry showed that the eNOS protein expression of the drug group was 11.1 +/- 1.9, significantly higher than that of the control group (5.6 +/- 0.6, P < 0.01). Western blotting showed that the eNOS protein expression of the drug group was 37.5 +/- 6.2, significantly higher than that of the control group (10.4 +/- 2.7, P < 0.01). The NO level of the drug group was 279 micromol/L +/- 72 micromol/L. significantly higher than that of the control group (60 micromol/L +/- 57 72 micromol/L, P = 0.01). CONCLUSION: Stent coated with diallyl trisulfide promotes the endothelialization and expression of eNOS, and raises the NO level. While promoting the recovery of the endothelial structure, stent coated with diallyl trisulfide promotes the recovery of endothelial function.