[Curative effects on standardized management of community patients with coronary heart disease complicated with chronic heart failure].

OBJECTIVE: To explore the effects on the standardized management of patients with coronary atherosclerotic heart disease complicated with chronic heart failure. METHODS: A total of 823 patients discharged from our department were randomly enrolled. Among 734 patients with follow-up consents, they were divided into management and control groups (n = 440, 294). The management group received standardized out-of-hospital management, regular health education and follow-ups of telephone and outpatient visits. RESULTS: Compared with the control group, the management group had lower rates of all-cause mortality, cardiac death and readmission due to cardiovascular events (CVE) declining by 26.5%, 32.2% and 57.0% respectively. Over a 4-year period, the annular survival rate of management group was 92%, 85%, 83% and 82% while that of control group 95%, 89%, 82% and 75% respectively. Patient compliance of digoxin and diuretics in the control group was inferior to that in the management group. CONCLUSION: Through standardized out-of-hospital management, the patients with coronary atherosclerotic heart disease plus chronic heart failure may achieve significant benefits through reducing the rates of all-cause mortality, cardiac death and readmission due to CVE and improving survival rate.

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1.

AIM: To explore the effect of neferine on angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. METHODS: Human umbilical vein smooth muscle cells (HUVSMCs) were used. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. Heme oxygenase (HO)-1 protein expression was tested by Western blot analysis. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation was determined by using immunoblotting. RESULTS: Pre-incubation of HUVSMCs with neferine (0.1, 0.5, 1.0, and 5.0 micromol/L) significantly inhibited Ang II-induced cell proliferation in a concentration-dependent manner and neferine 5.0 micromol/L increased HO-1 expression by 259% compared with control. The antiproliferative effect of neferine was significantly attenuated by coapplication of zinc protoporphyrin IX (ZnPP IX, an HO-1 inhibitor) with neferine. Ang II-enhanced ERK1/2 phosphorylation was markedly reversed by neferine. By inhibiting HO-1 activity with ZnPP IX, the inhibitive effect of neferine on ERK1/2 phosphorylation was significantly attenuated. Cobalt-protoporphyrin (CoPP), an HO-1 inducer, significantly decreased Ang II-induced ERK1/2 phosphorylation and inhibited Ang II-induced cell proliferation. The ERK1/2 pathway inhibitor PD98059 significantly blocked Ang II-enhanced ERK1/2 phosphorylation and inhibited cell proliferation. CONCLUSION: These findings suggest that neferine can inhibit Ang II-induced HUVSMC proliferation by upregulating HO-1, leading to the at least partial downregulation of ERK1/2 phosphorylation.

[Management of coronary atherosclerotic heart disease through an alliance of community and hospital].

OBJECTIVE: To evaluate the effect of out-hospital normalized management of coronary heart disease (CAD) on the end point events such as mortality, readmission, etc, and on the compliance of patients through normalized management by an alliance of community and hospital. METHODS: The samples were comprised of a total of 2000 patients in 15 communities. And 1642 patients agreed to a follow-up and signed a consent form. Ten communities were chosen as the intensive management group in which community clinicians were trained and the patient management plan was proposed and carried out. The remaining 5 communities were taken as the control group in which the community clinicians were not trained and the patients received only general management. Both groups received a follow-up of 23 months. RESULTS: Compared with the control group, the intensive manage group showed a lower risk of all-cause death, cardiac death and readmission due to cardiovascular events (CVE). They declined by 36.5% (OR 0.635, 95%CI 0.478-0.854), 41.5% (OR 0.585, 95%CI 0.428-0.800) and 56.1% (OR 0.439, 95%CI 0.315-0.612) respectively. The proportion of patients with NYHA III in the intensive management and control groups increased by 3.6% and 7.7% while that of the counterparts of NYHAIV in two groups increased by 1.6% and 6.4% respectively. The cardiac function in the patients of intensive management group was significantly superior to that in control group. Patients in both groups displayed an acceptable compliance to cardiac medications except for aspirin. The proportion of aspirin in the intensive management and control groups increased by 8.4% and 8.7% respectively (P<0.05). CONCLUSION: Through normalized management provided by an alliance of community and hospital, the rates of all-cause death and readmission due to CVE decrease significantly concurrently with an improvement of cardiac function and quality of life in CAD patients.

[Mechanism of cardioprotection induced by noninvasive limb ischemic preconditioning].

OBJECTIVE: To verify the inhibitory effect of mitochondrial calcium uniporter in remote preconditioning-induced cardioprotection. METHODS: By occlusion and reperfusion of left anterior descending artery, the rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vivo. Thus the ischemic reperfusion model was established. The rats were randomly assigned to undergo one of the following maneuvers: (1) remote preconditioning; (2) ruthenium red (an inhibitor of mitochondrial calcium uniporter); (3) spermine or SB202190 (an opener of mitochondrial calcium uniporter). Remote preconditioning was elicited by three cycles of 5 min of right femoral artery occlusion interspersed with 5 min of reperfusion. The mean arterial blood pressure, heart rate and lactate dehydrogenase released in plasma were measured during reperfusion but the infarct size was measured after reperfusion. RESULTS: In comparison with I/R group, remote preconditioning limited infarct size [(20.4 +/- 2.5)% vs (51.0 +/- 6.0)%] and lactate dehydrogenase release [(271 +/- 9) U/L vs (339 +/- 39)U/L] during reperfusion. On the contrary, spermine or SB202190 attenuated the reduction of infarct size and lactate dehydrogenase release induced by remote preconditioning. The group of spermine was [(40.8 +/- 9.2)% vs (20.4 +/- 2.5)%] and [(383 +/- 43) U/L vs (271 +/- 9) U/L] while the group of SB202190 was [(44.3 +/- 6.8)% vs (20.4 +/- 2.5)%] and [(356 +/- 26) U/L vs (271 +/- 9) U/L]. CONCLUSION: Inhibition of mitochondrial calcium uniporter opening is involved in the remote preconditioning-induced cardioprotection.

[Changes of serum hepatocyte growth factor before and after percutaneous coronary intervention in patients with unstable angina pectoris and significance there].

OBJECTIVE: To investigate the effect of unfitrate heparin (UFH) and low molecular weight heparin (LMWH) on the expression of serum hepatocyte growth factor (HGF) during percutaneous coronary intervention (PCI). METHODS: Seventy patients with chronic unstable angina pectoris were divided into 2 groups: PCI group (n = 49, with at least one main coronary artery branch with stenosis > or = 70%) and non-PCI group (n = 21, with the main coronary artery branch with stenosis < 70%). UFH was used at the beginning of coronary angiography in both groups and LMWH was used after PCI only in the PCI group. The serum level of HGF was measured before, during, and 1 and 7 days after PCI; and cardiac troponin 1 (cTnI) was measured before and 1 day after PCI in all 70 patients. RESULTS: The serum level of HGF of the PCI group increased during and immediately after PCI (12 322 +/- 3723 ng/L and 13 566 +/- 3767 ng/L respectively), both significantly higher than that before the procedure (1736 +/- 604 ng/L, both P < 0.0001), The serum level of HGF of the non-PCI group increased during and immediately after the procedure (10 928 +/- 2196 ng/L and 11 457 +/- 2298 ng/L respectively), both significantly higher than that before the procedure (967 +/- 349 ng/L, both P < 0.01). However, there were no significant differences in the HGF levels during and after the procedure between the PCI and non-PCI groups. The serum HGF returned to the normal level 24 h after the procedure in both groups. The serum GHF 7 days after the procedure of the cTnI (-) PCI group was significantly lower than that before the procedure (P < 0.01), however, the serum GHF 7 days after the procedure of the cTnI (+) PCI group remained relatively high, not significantly different from that before the procedure. CONCLUSION: There is an enhanced secretion of cardiac HGF in the patients with severe coronary artery disease. UFH promotes the release of serum HGF in the patients with chronic unstable angina pectoris undergoing PCI, which indicates some other biological effects in addition to its anticoagulant property. The delayed fall of serum HGF after PCI has relationship with minor myocardial infarction.

Relationship between hs-CRP, proMMP-1, TIMP-1 and coronary plaque morphology: intravascular ultrasound study.

BACKGROUND: Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of the acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. Little studies have focused on this field. Therefore we investigated the relationship between hypersensitive C-reactive protein (hs-CRP), pro-matrix metalloproteinase-1 (proMMP-1), tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and coronary plaque morphology. METHODS: Intravascular ultrasound (IVUS) examination was done in 152 patients with confirmed coronary heart disease before percutaneous coronary intervention from February 2003 to July 2005. Plasma samples of arterial blood were collected prior to the procedure. The level of hs-CRP, proMMP-1 and TIMP-1 were respectively measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Unstable and ruptured plaque were found more frequently in patients with acute myocardial infarction and unstable angina. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in ruptured and unstable plaque group. Positive remolding, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in ruptured and unstable plaque group. The levels of plasma hs-CRP, proMMP-1 and TIMP-1 were higher in ruptured plaque group. hs-CRP > 8.94 mg/L was used to predict ruptured plaque with a ROC curve area of 0.76 [95% confidence interval (CI), 67.0% - 85.8%], sensitivity of 71.8%, specificity of 77.0% and accuracy of 69.2% (P < 0.01), similarly for proMMP-1 > 0.12 ng/ml with a ROC curve area of 0.69 [95% CI, 58.2% - 80.2%], sensitivity of 69.2%, specificity of 75.2% and accuracy of 66.2% (P < 0.01), and TIMP-1 > 83.45 ng/ml with a ROC curve area of 0.67 [95% CI, 56.2% - 78.3%], sensitivity of 66.7%, specificity of 61.9% and accuracy of 66.2% (P < 0.01). CONCLUSION: The plaque characteristics correlate with the clinical presentation. The elevation of hs-CRP, proMMP-1 and TIMP-1 are related to the plaque instability and rupture.

[Puerarin suppresses the proliferation of vscular smooth muscule cells and c-fos and bcl-2 protein expression].

OBJECTIVE: To observe the role of puerarin on the proliferation of vascular smooth muscle cells(VSMC) induced by thrombin (T) and the effect of puerarin on the c-fos and bcl-2 protein expression. METHOD: Cell number and cell cycle analysis using flow cytometry were adopted as two different indicators of effects on proliferation of VSMC. Western blot was used to indicate the changes of c-fos and bcl-2 protein after 24 h of treatment of T and puerarin. RESULT: 1.5 x 10(-5) - 1.5 x 10(-3) mol x L(-1) puerarin could significantly suppress this stimulation of VSMC proliferation and DNA synthesis induced by T. Western blot demonstrated that after 24 hour of treatment with T and puerarin, T could significantly increase c-fos and bcl-2 protein and 1.5 x 10(-5) - 1.5 x 10(-3) mol x L(-1) puerain could significantly suppress this increase. CONCLUSION: puerarin can suppress the proliferation and DNA synthesis of VSMC promoted by T. This inhibitory effects of puerarin are closely related with the suppression of c-fos and bcl-2 protein.

Immortalization of human umbilical vein endothelial cells with telomerase reverse transcriptase and simian virus 40 large T antigen.

OBJECTIVE: To establish normally conditionally-immortalized human umbilical vein endothelial cells (HUVECs) by ectopic expression of the human telomerase catalytic enzyme (hTERT) and simian virus 40 large T (SV40 LT) antigen. METHODS: Primary HUVECs were transfected with recombinant retrovirus containing hTERT or SV40 LT respectively. Subsequently drug resistant cell clones were screened and expanded for further studies. Endothelial cell biomarkers were confirmed by examination. RESULTS: The morphological phenotype of the transfected cells was similar to the non-transfected cells. Von Willebrand factor, hTERT and SV40 LT could be detected in transfected HUVECs. Moreover, higher telomerase activity in transfected cells was maintained for over 50 population doublings compared with only low level of endogenous telomerase transiently at early population doublings in primary HUVECs. When exposed to TNF-alpha (tumor necrosis factor-alpha), the expression of E-selectin in transfected cells was significantly up-regulated, but no alteration of endothelial lipase was found. CONCLUSION: Ectopic coexpression of hTERT and SV40 LT can effectively immortalize HUVECs without tumorigenicity in vitro. Immortalized HUVECs may be an ideal target of further molecular function studies.

[The evaluation on stent implantation efficacy of myocardial bridge and severe atherosclerosis lesions in the segments proximal to the myocardial bridge].

OBJECTIVE: To assess long term stent implantation efficacy of myocardial bridge and severe atherosclerosis lesions in the segments proximal to the myocardial bridge. METHODS: The study population consisted of 3 groups (103 patients). Group A included 28 patients with severe atherosclerosis lesion of luminal narrowing of > or = 70% in the segments proximal to the myocardial bridge. Group B included 16 patients with symptomatic myocardial bridge lesion of systolic luminal narrowing of > or = 95%. Group C included 59 patients with severe atherosclerotic lesion of luminal narrowing of > or = 70%. All lesions were successfully treated with stent by standard interventional techniques. Quantitative coronary angiography was performed before and immediately after stent deployment. Follow-up Quantitative coronary angiography was performed at six months or later. Clinical evaluation was done at 20 months after PCI. RESULTS: There was no significant difference in luminal diameter and stent diameter among 3 groups immediately after stent implantation (P > 0.05). At six months, restenosis occurred in 4 patients in Group A (14.3%), in 7 patients in Group B (43.7%), and in 8 patients in Group C (14.8%), respectively. The rate of restenosis was significantly lower in group A and C than in group B (P < 0.05). No significant difference was found between group A and C. Additional balloon dilating of stent were performed in all restenosis patients. Clinical evaluation at 20 months showed that all patients remained free of angina and cardiac events. CONCLUSION: The efficacy of intracoronary stent implantation in treating severe atherosclerosis lesion in the segments proximal to the myocardial bridge is not affected by abnormal haemodynamic changes of myocardial bridges. The rate of restenosis in intracoronary stent implantation of myocardial bridges is higher than that of atherosclerotic lesions in the segments proximal to myocardial bridge.

[Immortalization of human umbilical vein endothelial cells by transfected with hTERT and SV40LT].

OBJECTIVE: To immortalize human umbilical vein endothelial cells (HUVECs) by ectopic expression of the telomerase reverse transcriptase enzyme (hTERT), and by Simian Virus 40 Large T (SV40LT) antigen without malignant transformation. METHODS: Two different retroviruses that contained hTERT/SV40LT cDNA fragment and drug resistance gene were constructed, and were used to transfect normal primary HUVECs. The transfected cells were screened with 500 microg/ml G418 and 4 microg/ml puromycin. Drug resistance cell clones were selected 3 days after transfection and cultured for further studies. An under inverted microscope and a scanning electron microscope were used to observe the morphology and growth of the cells. The expression of VIII factor and transfected DNA fragments were detected for identification of the endothelial origin and successful transfection. And the expression of E-selectin and endothelial lipase with or without the stimulus of TNF-alpha were also assayed to analyze the biological activity of the transfected cells. RESULTS: The cells were homogenous, closely apposed, large, flat, and polygonal, displayed a characteristic ovoid nucleus with one or two nucleoli and formed monolayer with polygonal shape without overlapping. Immunocytochemical staining showed the existence of VIII factor. SV40LT/hTERT antigen expressed by the transfected cells was detected, while the contrasts had non-expression. Telomerase activity of the cell was detected in the transfected cells, which was 0.36 at 12 th passage and 0.38 at 50 th passage. However, the activity in the normal HUVECs was 1.12 at the first passage and 0.06 at the third passage assayed by PCR-ELISA. Both E-selectin and endothelial lipase were all specific in endothelial cells. The expressions of these two were also detected. And the expression of E-selectin can be up-regulated with the stimulus of TNF-alpha, while the expression of endothelial lipase was not unregulated significantly. CONCLUSION: Ectopic expression of hTERT and SV40LT can effectively immortalize HUVECs without tumorigenesis.

Interleukin-18 levels on admission are associated with mid-term adverse clinical events in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.

The long-term prognostic value of interleukin (IL)-18 in patients with ST-segment elevation acute myocardial infarction (STEMI) has been conflicting. Thus, the purpose of this study was to test whether the level of interleukin-18 measured on admission can predict long-term adverse clinical events in patients with STEMI who were undergoing percutaneous coronary intervention (PCI). We recruited 288 consecutive STEMI patients (210 men, average age [71.42 +/- 10.32] years) with onset < 6 hours who were undergoing primary PCI, and 148 age- and gender-matched control subjects. Plasma levels of IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) in all subjects. The patients with STEMI were then followed prospectively over 434 days (range, 0 to 642 days) for the occurrence of composite major adverse clinical events (MACE) (cardiac mortality, recurrent myocardial infarction, or readmission due to advanced heart failure). Patients with STEMI exhibited higher levels of plasma IL-18 (P < 0.001) compared with the control subjects. Positive correlations between IL-18 and cardiac troponin-I (cTnI) (r = 0.353, P = 0.0004) and IL-18 and high-sensitivity C-reactive protein (hs-CRP) (r = 0.420, P < 0.001) were observed by Spearman's correlations analysis. Logistic regression analysis demonstrated that IL-18 >/= 450 pg/mL (OR 10.854, 95% CI 2.328 to 50.594, P < 0.0001) was a significant independent predictor of composite MACE at 60 days. Cox regression analysis demonstrated that high plasma IL-18 levels were not correlated with the occurrence of long-term composite MACE. The level of plasma IL-18 on admission may predict 60-day adverse clinical outcome, but not the long-term adverse clinical events in patients with STEMI undergoing PCI, and may be useful for mid-term risk stratification.

Influence of granulocyte colony-stimulating factor on cardiac function in patients with acute myocardial infarction and leukopenia after revascularization.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) seems to improve cardiac function and perfusion when used systemically through mobilization of stem cells into peripheral blood, but results of previous clinical trials remain controversial. This study was designed to investigate safety and efficacy of subcutaneous injection of G-CSF on left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction (STEMI). METHODS: Thirty-three patients (22 men; age, (68.5 +/- 6.1) years) with STEMI and with comorbidity of leukopenia were included after successful primary percutaneous coronary intervention within 12 hours after symptom onset. Patients were randomized into G-CSF group who received G-CSF (10 microg/kg of body weight, daily) for continuous 7 days and control group. Results of blood analyses, echocardiography and angiography were documented as well as possibly occurred adverse events. RESULTS: No severe adverse events occurred in both groups. Mean segmental wall thickening in infract segments increased significantly at 6-month follow up compared with baseline in both groups, but the longitudinal variation between two groups had no significant difference (P > 0.05). The same change could also be found in longitudinal variation of wall motion score index of infarct segments (P > 0.05). At 6-month follow-up, left ventricular end-diastolic volume of both groups increased to a greater extent, but there were no significant differences between the two groups when comparing the longitudinal variations (P > 0.05). In both groups, left ventricular ejection fraction measured by echocardiography ameliorated significantly at 6-month follow-up (P < 0.05), but difference of the longitudinal variation between two groups was not significant (P > 0.05). When pay attention to left ventricular ejection fraction measured by angiocardiography, difference of the longitudinal variation between groups was significant (P = 0.046). Early diastolic mitral flow velocity deceleration time changed significantly at 6- month follow-up in both groups (P = 0.05). CONCLUSIONS: Mobilization of stem cells by G-CSF after reperfusion of infarct myocardium is safe and seems to offer a pragmatic strategy for recovery of myocardial global function.