[Effect of Astragalus polysaccharides on the phenotype and functions of human dendritic cells in vitro].

OBJECTIVE: To assess the effect of astragalus polysaccharides (APS) in inducing phenotypic and functional changes of human dendritic cells (DCs) in vitro. METHODS: Human dendritic cells were induced from the peripheral blood monocytes in vitro by the application of tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) and GM-CSF, and cultured in the presence of APS at different concentrations (50, 100, and 200 mg/L). The morphological changes of the DCs were identified by optical microscope or scanning electron microscope. The phenotypic alterations of the cells were analyzed by flow cytometry. RESULTS: The DCs cultured for 24 h in the presence of LPS and APS at 50 and 100 mg/L showed suspended growth in the culture medium and underwent morphological changes from spherical cells to irregular cells, with rough cell surface and cell processes of different morphologies. APS-treated DCs had the most typical dendritic structures and highly expressed the phenotypic markers of DCs (CD86 and HLA-DR), but with down-regulated CD14 expression as shown by flow cytometry. CONCLUSION: Both APS and the cytokines can induce the maturation of DCs derived from peripheral blood monocytes.

[Association of dendritic cell distribution with intima hyperplasia in rats with diabetes mellitus].

OBJECTIVE: To investigate the association of dendritic cell distribution in the peripheral blood, spleen and arterial wall with intimal hyperplasia in rats with diabetes mellitus. METHODS: Diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin and high-fat feeding for 8 weeks. Peripheral blood, arterial wall and the spleen were collected from the rats to prepare cell suspensions, in which the proportions of dendritic cells and T cells were determined by flow cytometry. RESULTS: The tunica intimal hyperplasia was more obvious in diabetic rats with or without high-fat feeding as compared with that of the control rats (P<0.05), and their dendritic cells decreased significantly in the peripheral blood (P<0.05) but increased in the arterial wall. The percentage of T cells was also increased in the peripheral blood and arterial wall of the diabetic rats. CONCLUSION: Changes in the distribution of dendritic cells and T cells are closely associated with intimal hyperplasia in diabetic rats, suggesting the involvement of dendritic cells and T cells in the formation of atherosclerosis.

[Efficacy and safety of implantation of multiple drug-eluting stents].

OBJECTIVE: To assess the efficacy and safety of implantation of multiple drug-eluting stents. METHODS: A retrospective study of 151 cases was conducted, including 34 with implantation of at least 3 drug-eluting stents in the coronary artery (MS group), 53 with implantation of two stents (TS group), and 64 with a single stent (OS group). The incidence of major adverse cardiovascular event (MACE) and restenosis was evaluated. RESULTS: No significant difference was found between the 3 groups in the incidence of MACE or in the stent thrombosis rate 30 days after the implantation. Follow-up of the patients for 6 months still showed comparable restenosis rate and MACE incidence between the 3 groups. CONCLUSION: Implantation of multiple drug-eluting stents does not increase the risk of restenosis or MACE, and has comparable safety and efficacy with implantation of single and two stents.

[Effect of enalapril on diabetic rat myocardial ultrastructure].

OBJECTIVE: To observe the changes in the myocardial ultrastructure of diabetic rats and the effect of enalapril treatment. METHODS: Male Wistar rats were divided into 3 groups, namely the control group, diabetic group and enalapril intervention group. Diabetes was induced with peritoneal injection of streptozotocin in the latter 2 groups, and in enalapril group, the rats were treated with enalapril at the daily oral dose of 2 mg/kg for 1, 3 and 5 months after streptozotocin injection. Histological analysis of the left ventricular tissue was performed with transmission electron microscope 1, 3, and 5 months after establishment of diabetes. RESULTS: Onset of myocardial damages was observed 1 month after the development of diabetes in the rats with gradual time-dependent exacerbation. Enalapril treatment could partially reverse the myocardial destruction in the diabetic rats. CONCLUSION: Enalapril intervention may improve the ultrastructural pathology of the myocardium in diabetic rats, which is suggestive of the action mechanisms of angiotensin-converting enzyme inhibitors in myocardium preservation.

[Changes of CD4+CD28- T cell and CD4+CD25+ regulatory T cell subsets in patients with coronary heart disease].

OBJECTIVE: To investigate the changes of CD4(+)CD28(-) T cell and CD4(+)CD25(+) regulatory T cell (Treg) subsets in patients with coronary artery disease (CAD). METHODS: Twenty-eight patients with angiographically established CAD were recruited in this study, including 16 with unstable angina (UA group) and 12 with stable angina (SA group). Eleven patients with chest pain syndrome served as the control group. The proportions of peripheral CD4(+)CD28(-) T cells and CD4(+)CD25(+) Treg subsets were determined with fluorescence-activated cell sorting (FACS). RESULTS: The proportions of CD4(+)CD25(+) Treg were significantly lower in UA group (6.55-/+2.45%) than in SA (14.01-/+4.92%) and control groups (13.55-/+3.87%). The proportions of CD4(+)CD28(-) T cells were significantly higher in UA group (10.55-/+4.76%) than in SA (2.64-/+1.33%) and control (2.75-/+1.55%) groups. CONCLUSION: Alterations of circulating T-lymphocyte subsets occur in patients with UA. The changes of Treg and CD4(+)CD28(-) T cells may lead to breakdown of peripheral autoimmune tolerance and play an important role in the development and progression of CHD.

[Effects of proadrenomedullin N-terminal 20 peptide on angiotensin II-induced NO production in rat cardiac fibroblasts].

OBJECTIVE: To explore the effects of proadrenomedullin N-terminal 20 peptide (PAMP) on nitric oxide (NO) production in rat cardiac fibroblasts (CFs) induced by angiotensin II (AngII) stimulation. METHODS: Neonatal SD rat CFs isolated by trypsin digestion were cultured and stimulated with PAMP, AngII or their combination, and NO production in the CFs in response to the treatments was measured by nitric acid reductase method. RESULTS: NO levels in the cell culture treated with 1x10(-9), 1x10(-8), 1x10(-7), and 1x10(-6) micromol/L AngII were 73.88-/+2.23, 64.34-/+3.02, 54.12-/+2.82, and 40.21-/+1.45 micromol/L, respectively, showing significant differences between the groups (P<0.01), whereas treatment of the cells with 1x10(-9), 1x10(-8), 1x10(-7), and 1x10(-6) micromol/L PAMP did not result in significant variation in NO production (74.40-/+3.42, 74.91-/+2.66, 75.77-/+3.31, and 74.23-/+2.43 micromol/L, respectively) in comparison with that of the blank control group (74.57-/+2.49 micromol/L, P>0.05). Combined treatments with 1x10(-7) micromol/L AngII and PAMP at 1x10(-9), 1x10(-8), 1x10(-7), and 1x10(-6) micromol/L PAMP caused significant increment of NO production (66.15-/+2.95, 80.58-/+3.77, 88.67-/+1.46, and 96.22-/+2.96 micromol/L, respectively, P<0.01) in a PAMP dose-dependent manner, suggesting the abolishment of AngII-induced enhancement of NO production in the CFs by PAMP. CONCLUSION: PAMP increases NO production in the CFs in the presence of AngII but it does not induce significant changes in NO production when used alone.

[Effect of urotensin II on secretion of adrenomedullin from human vascular endothelial cells].

OBJECTIVE: To study the effect of human urotensin II (HU II) on secretion of adrenomedullin (ADM) from human vascular endothelial cells (HVEC) and its mechanism. METHODS: In cultured HVEC, different concentrations of HUII were used to stimulate the ADM secretion from HVEC, and the inhibitors of different signal transduction pathway were used to investigate their effects on ADM secretion. The contents of ADM in medium were determined by radio immunoassay. RESULTS: HUII stimulated secretion of ADM from HVEC in a time-dependent and concentration-dependent manner. The contents of ADM in the experiment groups were changed compared with that in control group (P < 0.05). The increase of ADM could be inhibited by inhibitor of extracellular signal-regulated protein kinase (PD(98059)), inhibitor of P38 kinase (SB(202190)), inhibitor of calmodulin (W(7)) and inhibitor of Ca(2+) (nicardipine) (P < 0.05). The inhibition ratio in those groups was 68%, 78%, 24% and 25% respectively. But the inhibitor of Calcineurin (CaN) and inhibitor of protein kinase C (H(7)) had no influence on the secretion of ADM from HVEC (P > 0.05). CONCLUSION: The stimulated effect of HUII on the ADM secretion from HVEC may be mediated by Ca(2+), ERKs, CaM-PK and P38 signal transduction pathways.

[Dynamic changes in plasma adrenomedullin levels and effect of enalapril intervention in diabetic rats].

OBJECTIVE: To observe the dynamic changes of plasma adrenomedullin (ADM) levels and the effect of enalapril intervention in diabetic rats. METHODS: Fifty-two wistar rats were grouped into 1- and 3-month groups (7 each), both including a control and a streptozotocin-induced diabetic group. The 5-month group was divided into control, diabetic and enalapril-treatment diabetic groups (8 each, the last group receiving oral enalapril treatment at the daily dose of 2 mg/kg from the first to the fifth month after diabetes induction). Blood samples were collected from the heart of the rats at the end of 1, 3 and 5 months for determination of plasma ADM concentrations radioimmunoassay. RESULTS: Plasma ADM levels were significantly higher in diabetic rats than in the corresponding control rats in 1- and 3-month groups. ADM levels in the diabetic rats of 5-month group were significantly decreased in comparison with that of 1- and 3-month groups. In 5-month group, plasma ADM levels of enalapril-treated diabetic rats elevated significantly in comparison with that in the control rats and the diabetic rats without enalapril treatment. CONCLUSION: ADM may play an important role in the pathophysiology of diabetes.

[Changes of the new gaseous transmitter H2S in patients with coronary heart disease].

OBJECTIVE: To investigate the changes of plasma hydrogen sulfide (H(2)S) in patients with coronary heart disease (CHD). METHODS: Plasma H(2)S levels were measured in 40 patients with CHD and 17 angiographically normal patients by sulfide-sensitive electrodes, and the variation of plasma H(2)S levels was analyzed in different clinical types of CHD and in different types of coronary artery lesions. The association of plasma H(2)S levels with the risk factors of CHD was also analyzed. RESULTS: Plasma H(2)S levels were significantly lowered in CHD patients in comparison with that in angiographically normal control subjects (26.10+/-14.27 micromol/L vs 51.74+/-11.94 micromol/L, P<0.001). In CHD patients, plasma H(2)S levels in unstable angina patients (UAP, 23.60+/-14.41 micromol/L) and acute myocardial infarction patients (AMI, 19.98+/-7.516 micromol/L) were significantly lower than that in stable angina patients (SAP, 38.41+/-14.53 micromol/L, P<0.05). No significant difference in plasma H(2)S levels was found between CHD patients with double-vessel and multi-vessel lesions (16.91+/-7.98 vs 18.39+/-7.78 micromol/L, P>0.05), but the two groups of patients had significantly lower plasma H(2)S levels than patients with single-vessel involvement (33.04+/-15.01 micromol/L, P<0.05 and P<0.01, respectively). Plasma H(2)S level was significantly lower in CHD patients with coronary artery occlusion than in patients with simple stenosis (19.04+/-9.55 vs 28.24+/-14.85 micromol/L, P<0.05). Among the CHD patients, H(2)S levels were significantly lower in smokers than in non-smokers (27.54+/-10.37 vs 32.24+/-15.77 micromol/L, P<0.05), also lower in hypertensive patients than in normotensive patients (20.36+/-8.69 vs 33.77+/-15.86 micromol/L, P<0.01). Plasma H(2)S levels showed a significant inverse correlation with blood glucose (r=-0.493 6, P=0.001 6), but there were no significant correlations with sex, age, cholesterol, triglyeride, TC, low-density lipoprotein, high-density lipoprotein, or body mass index. CONCLUSION: Decreased plasma H(2)S levels may correlate with the severity of CHD and changes of the coronary artery, and may implicate the risk factors of CHD such as smoking, hypertension, and high blood glucose.

[Mechanism of urotensin II-stimulated adrenomedullin secretion in human vascular endothelial cells].

OBJECTIVE: To study the mechanism of urotensin II(U II)-stimulated adrenomedullin secretion in human vascular endothelial cells. METHODS: In cultured human vascular endothelial cells (HEVCs), different concentrations of U II was used to stimulate the secretion of Adm, and different inhibitors were used to study the changes in the secretion after block of different signal transduction pathways. The contents of Adm in the medium were detected with radioimmunoassay. RESULTS: U II-stimulated Adm secretion in the HEVCs in a time- and concentration-dependent manner. Adm contents of the treatment groups were comparable with that of the control group (P<0.05 ), and the secretion of Adm could be inhibited by the inhibitor of extracellular signal-regulated protein kinases (PD098059), p38 kinase inhibitor (SB202190), calmodulin inhibitor (W7) and Ca(2+) inhibitor (nicardipine)(P<0.05), but calcineurin inhibitor and protein kinase C inhibitor (H7) had no such effect (P>0.05). CONCLUSION: Ca(2+), MAPK, CaM-PK and p38 signal transduction pathways may play major roles in U II-stimulated secretion of Adm in HVECs.

[Effect of percutaneous intervention on adrenomedullin and tumor necrosis factor in the coronary circulation].

OBJECTIVE: To evaluate the effect of percutaneous intervention (PCI) on coronary circulation levels of adrenomedullin (ADM) and tumor necrosis factor alpha (TNF-alpha) in patients with coronary heart disease (CHD). METHODS: Thirty-three CHD patients underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting (altogether 48 stents were implanted). Blood samples were collected from the coronary sinus and femoral artery at the time points of immediately before and after angioplasty, immediately after PTCA or stenting, 10 min after procedures, respectively. RESULTS: The ADM and TNF-alpha levels in the coronary sinus varied little after coronary angiography, but were elevated markedly following PTCA from the basal levels of 36.3+/-1.3 pg/ml to 28.9+/-1.9 pg/ml (P<0.01) and from 11.10+/-0.46 ng/ml to 8.84+/-0.37 ng/ml (P<0.01), respectively. Further increases of ADM and TNF-alpha levels were detected immediately after stent deployment. ADM recovered to basal levels 10 min after completion of the procedures, while TNF-alpha underwent further increase. Before the procedure, ADM and TNF-alpha levels were higher in the coronary sinus than in the femoral artery (28.9+/-1.9 pg/ml vs 22.6+/-0.8 pg/ml, P<0.01; 8.84+/-0.37 ng/ml vs 7. 56+/-0.23 ng/ml, P<0.01, respectively), and their levels in the femoral artery did not undergo significant changes in response to the operations. CONCLUSION: The coronary circulation levels of ADM and TNF-alpha increase after PTCA and stenting but not after coronary angiography in CHD patients, which might be attributed to injuries by the procedures as well as the mechanical stimulation by the stent.

[Clinical study of plasma urotensin II in patients with coronary heart disease].

OBJECTIVE: To investigate the changes in plasma urotensin II(U II) expression levels in patients with coronary heart disease (CHD). METHODS: Plasma U II levels in 50 CHD patients with coronary stenosis indicated by coronary angiography and 20 healthy subjects were determined by radio immunoassay. RESULTS: Venous plasma U II levels were significantly lowered in CHD patients in comparison with the healthy subjects (1.61+/-1.02 pg/ml vs 3.70+/-1.30 pg/ml, P=0.000). In the CHD patient group, significantly differences were noted in the U II levels between patients with stable angina (2.62+/-1.20 pg/ml), unstable angina (1.39+/-0.80 pg/ml) and acute myocardial infarction (AMI, 1.04+/-0.45 pg/ml, P=0.004). CHD patients with coronary artery occlusion and those with only coronary stenosis had comparable venous plasma U II levels (1.29+/-1.02 pg/ml vs 1.76+/-1.00 pg/ml, P=0.131), whereas the patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) had higher U II levels than the other subjects in the CHD patient group (2.28+/-0.94 pg/ml vs 1.40+/-0.96 pg/ml, P=0.008), and the femoral plasma U II levels were significantly elevated after PTCT, increasing from 1.18+/-1.14 pg/ml to a postoperative level of 2.22+/-1.77 pg/ml (P=0.001). CONCLUSION: U II might play a role in the pathophysiological process of CHD and can be involved in the restenosis after angioplasty.

[Expression of urotensinII in human coronary artery and coronary atherosclerosis].

OBJECTIVE: To assess the expression intensity of urotensinII (UII) in normal and atheromatous human coronary artery and explore its significance in coronary atherosclerosis. METHODS: Specimens of coronary arteries were obtained from 5 normal subjects and the expression of human UII in the specimens was detected by immunohistochemical method. RESULTS: UII expression was found in the endothelial cells (ECs), foam cells (FCs), inflammatory cells (ICs) and intima smooth muscle cells (ISMs) of human coronary artery. Even in the normal coronary artery, UII expression could be detected immunohistochemically in the ECs, which, however, was characterized by higher UII expression levels in fatty streak lesions but by almost normal levels in fibrous and atheromatous plaque in the coronary artery. Enhanced UII expression was observed in FCs and ICs when fibrous plaque and atheromatous plaque developed in comparison with that in fatty streak lesions. The ISMs in all the lesions had mild UII immunoreactivity, but as the atherosclerosis exacerbated, the immunoreactivity tended to intensify. CONCLUSION: Human UII may regulate the functions of ECs, FCs, ICs and ISMs in the development and progression of coronary atherosclerosis.

[Clinical study of changes of urotensin II in patients with congestive heart failure].

OBJECTIVE: To investigate the changes of plasma urotensinII (UII) levels in patients with congestive heart failure (CHF) of different severities and their clinical implications. METHODS: Plasma UII was determined by radioimmunoassay in 45 patients with CHF and 20 healthies control subjects. In all the subjects, the left ventricular fraction (LVEF) and the ratio of E/A were measured by echocardiography. RESULTS: The plasma UII level was significantly lowered in CHF patients in comparison with that in control subjects (1.41+/-1.09 pg/ml vs 4.35+/-1.22 pg/ml, P=0.000). A significant correlation of plasma UII level with LVEF (r=0.540, P=0.000) and the E/A ratio was observed (r=0.539, P=0.000), and the severity of CHF was shown to be inversely correlated with plasma UII levels in the patients (r=-0.656, P=0.000), which was elevated after treatment. CONCLUSION: UII might play a role in the pathophysiological process of CHF, and its plasma level may serve as an indicator of the severity of CHF.

Changes of plasma adrenomedullin and proadrenomedullin N-terminal 20 peptide concentrations in patients with heart failure.

OBJECTIVE: To study the changes in plasma adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) concentrations and their clinical significance in the pathological process of congestive heart failure (CHF). METHODS: Plasma ADM and PAMP concentrations in 45 patients with CHF (according to the functional classification of New York Heart Association, NYHA) and 20 control subjects were measured by specific radioimmunoassay. RESULTS: Plasma ADM concentrations were 51.464+/-.52 pg/ml and 70.39+/-3.22 pg/ml respectively in patients of NYHA class II and class III, which were significantly higher than those in control subjects (24.12+/-1.59 pg/ml, P<0.05 for both comparisons), while significant differences in plasma PAMP concentrations were not identified in the 2 groups of patients (6.24+/-1.71 pg/ml and 7.38+/-1.28 pg/ml, respectively) in comparison with the control level(8.56+/-2.44 pg/ml, P>0.05 for both comparisons). Patients of NYHA class IV, when compared with the 2 groups of patients mentioned above, had significantly decreased plasma ADM and PAMP concentrations (36.33+/-2.17 pg/ml and 2.79+/-0.89 pg/ml respectively, P<0.05 in both cases), but had higher plasma ADM and lower PAMP concentrations when compared with the control subjects, (P<0.05 respectively). CONCLUSION: The changes of plasma ADM and PAMP concentrations at different stages of CHF indicate intramolecular regulation disturbances of vasodilator peptides of proadrenomedullin, and ADM may play a more important role in the development of CHF.

[Relation of the ST-segment elevation pattern in acute phase of anterior wall acute myocardial infarction to short-term prognosis].

OBJECTIVE: To observe the relation of ST-segment elevation pattern of electrocardiogram (ECG) recorded in acute phase of anterior wall acute myocardial infarction (AMI) to short-term prognosis. METHODS: Sixty-two patients with first anterior wall AMI were divided into 3 groups according to ST-segment elevation pattern in lead V3 of a 12-lead ECG at admission. Patients in group A (n=18) were characterized by concave type of ST-segment elevation, group B (n=27) by straight type and group C (n=17) by convex type. The peak value of serum creatine phosphate kinase (CPK) and left ventricular ejection fraction (LVEF) were measured. The incidence of serious complications (including malignant arrhythmia, left ventricular dysfunction and cardiogenic shock) and mortality within the initial 4 weeks of hospitalization were recorded. RESULTS: The median value of peak CPK of the 3 groups was 2 014.4, 4 486.8 and 5 826.9 IU/L respectively, and the peak value of CPK in group A was much lower than that in groups B and C ( D<0.05 and P<0.01, respectively). LVEF measured by echocardiogram within 14 d after myocardial infarction were 61.2%, 48.6% and 38.7% respectively, showing significant difference between groups A and B and between groups B and C (P<0.05) as well as between group A and C (P<0.01). The incidences of serious complications and mortality within 4 weeks after AMI in group A were much lower than those in groups B and C (P<0.05), but there was no significant difference between groups B and C ( D>0.05). CONCLUSION: The shape of ST-segment elevation in lead V3 of a 12-lead ECG in acute phase of anterior wall AMI may reflect the severity of myocardial ischemic injury, and convex type of ST-segment elevation in lead V3 in acute phase often indicate poor short-term prognosis.

[Changes in plasma levels of adrenomedullin and cyclic adenosine monophosphate and their interrelation in patients with chronic heart failure].

OBJECTIVE: To investigate the changes in plasma levels of adrenomedullin (ADM) and cyclic adenosine monophosphate (cAMP) in patients with chronic heart failure (CHF) in an attempt to understand the role of ADM in the occurrence and development of CHF. METHODS: The plasma levels of cAMP and ADM were measured by radioimmunoassay in 45 patients with CHF (including 10 of NYHA classII, 15 of class III, and 20 of class IV) and 20 healthy controls respectively. RESULTS: Plasma ADM and cAMP levels significantly increased in patients of NYHA class II, III, and IV as compared with the healthy controls (P<0.05), with those of class III patients being the highest. Positive correlation between ADM and cAMP was noted in CHF patients(r=0.735, P<0.01). CONCLUSION: Plasma levels of ADM and cAMP were in close correlation with the degree of heart failure, varying dynamically with the development of heart failure. There was mutual accommodation between ADM and cAMP, and increased cAMP level partly results from elevated ADM level in CHF patients.