Effect of external counterpulsation on asymmetry diethylarginine and endothelin levels in blood

AIM:To observe changes of serum asymmetry dimethylarginine (ADMA) and endothelin-1 (ET-1) levels,which reflect blood vessel endothelial function,after therapy of enhanced external counterpulsation(EECP) in patients who had taken percutaneous transluminal coronary angioplasty and stent.METHODS:Fifty one coronary heart disease patients (all of them had taken percutaneous tranluminal coronary angioplasty and stent) were distributed into two groups by matching them with ratio of 1∶2,17 patients in EECP group and 34 patients in control group.Both of two groups were given conventional medicine,in addition,EECP group was undertaken three courses of treatment of EECP.ADMA was detected by HPLC-fluorescence method,and ET-1 was detected by radio-immunity method.RESULTS:In EECP group ，compared with prior treatment,ADMA and ET-1 levels was obviously reduced (P<0.05).In control group,compared with prior treatment,ADMA had no significant difference (P>0.05) and ET-1 was higher (P<0.01).Compared between two groups,extent of decrease in ADMA and ET-1 levels in EECP group were more obvious than control group (P<0.01).Improvement of angina and decrease of frequency of angina was more obvious in EECP group than control group.Besides,decrease of ADMA level was positive correlation with them (r=0.85，0.70,respectively P<0.01).CONCLUSION:EECP reduces serum ADMA and ET-1 levels by increasing shear stress to vessel endothelium in coronary heart disease patients who had taken percutaneous tranluminal coronary angioplasty.It hints that EECP can improve endothelial function and provides experimental evidence for the combined treatment of coronary heart disease.     

Effects of Ca2+on the releases of ET-1, NO and PGI2 from bovine coronary artery endothelial cells during hypoxia

AIM: To explore the mechanism of ET-1, NO and PGI² release from coronary artery endothelial cells(CAEC) induced by acute hypoxia. METHODS: Bovine coronary artery endothelial cells were cultured and [⁴⁵ Ca²⁺] was used to investigate the difference of calcium uptake between normoxia group and hypoxia group(3% O₂). The contents of ET-1, NO and PGI² in media of normoxia group, hypoxia group and hypoxia + verapamil group were measured 24 h after hypoxia. RESULTS: [ ⁴⁵ Ca²⁺] uptake by CAEC in hypoxia group was 1.9 times more than normoxia group(P< 0.01). Hypoxia + verapamil group released more PGI², ET-1 and less NO than hypoxia group(P< 0.05). CONCLUSION: Changes of ET-1, NO and PGI² releases during hypoxia may be caused by the inflow of Ca²⁺ into coronary artery endothelial cells.     

Impact of hydrogen sulfide donor on endothelin-1 and connective tissue growth factor expression in rats with pulmonary hypertension induced by high pulmonary blood flow

AIM: To explore the possible impact of hydrogen sulfide (H2S) donor-sodium hydrosulfide (NaHS) on endothelin-1 (ET-1) and connective tissue growth factor (CTGF) expressions in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Thirty-two male SD rats were randomly divided into 4 groups: shunt group, shunt+NaHS group, sham group and sham+NaHS group. Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. After 11 weeks of experiment, rat systolic pulmonary artery pressure (SPAP), lung tissue H2S, plasma ET-1 concentration and lung tissue ET-1mRNA expression, as well as pulmonary artery CTGF protein expression were detected.RESULTS: After 11 weeks of experiment, SPAP, lung tissue ET-1mRNA, plasma ET-1 as well as pulmonary artery CTGF expressions were increased markedly, respectively, whereas H2S in lung tissue decreased significantly in rats of shunt group as compared with that in sham group (all P<0.05). After administration of NaHS for 11 weeks, H2S in lung tissue increased significantly, whereas SPAP, plasma ET-1 and lung tissue ET-1 mRNA expression as well as pulmonary artery CTGF protein expression decreased significantly, respectively, in rats of shunt+NaHS group as compared with that in shunt group (all P<0.05).CONCLUSION: NaHS might be involved in the development of pulmonary hypertension induced by high pulmonary blood flow by down-regulating vasoactive peptides ET-1 and CTGF expressions in lung tissues of rats.     

Relationship between epicardial adipose tissue thickness and plasma N-terminal pro-B-type natriuretic peptide level in patients with stable coronary artery disease

AIM: To analyze the relationship between epicardial adipose tissue(EAT) thickness and plasma N-terminal pro-B-type natriuretic peptide(NT-proBNP) level in the patients with stable coronary artery disease.METHODS: The patients with chest pain(n=115) admitted to our hospital underwent coronary artery computer tomography and further underwent coronary angiography for confirming whether they had coronary artery disease. EAT thickness was evaluated at the right ventricular free wall imaged by coronary artery computer tomography. Plasma NT-proBNP level was examined by an automatic biochemistry analyzer.RESULTS: Eighty-one patients were confirmed to have stable coronary artery disease and thirty-four patients were excluded to have coronary artery disease. Left ventricular ejection fraction of these patients of 2 groups were all normal. The natural logarithm of plasma NT-proBNP level [ln(NT-proBNP)] of the patients with stable coronary artery disease was significantly higher than that of the patients without coronary artery disease(P<0.05). EAT thickness of the patients with stable coronary artery disease was also higher than that of the patients without coronary artery disease(P<0.05). EAT thickness was related to ln(NT-proBNP) positively(P<0.05). After adjustment of related impact factors, EAT thickness was still related to ln(NT-proBNP) positively(P<0.05). Multiple-factor regression analysis showed that EAT thickness was the independent influence factor on LnNT-proBNP(P<0.05).CONCLUSION: EAT thickness and plasma NT-proBNP level are both increased significantly and is related to each other in the patients with stable coronary artery disease.     

Relation between severe coronary stenosis lesion distribution and risk factors in young and middle-aged adults

AIM: To evaluate the classical and novel risk factors in young and middle-aged patients with coronary artery disease (CAD), and to analyze the relation between coronary risk factors and coronary lesion distribution. METHODS: A group of one hundred and eighty-nine patients, aged not more than 60 years with severe coronary stenosis on coronary angiography, and the other group of age-matched one hundred and sixty-one patients having normal or non-severe stenosis on coronary angiography were comprised in the study. Conventional factors (such as smoking, diabetes, hypertension, lipid spectrum and fasting plasma glucose) and novel risk factor (homocysteine) were compared between the groups. Moreover, the relation between the risk factors, and coronary lesion distribution including left main artery (LMA) or proximal or mid-left anterior descending (LAD) artery and remaining coronary lesions were investigated. Logistic regression analysis was used to define confounding factors for predicting severe CAD and coronary lesion distribution. RESULTS: Male and smoking were more prevalent in the group with severe coronary stenosis compared to the other group. The levels of homocysteine, triglyceride and apolipoprotein B were also higher in the group with severe coronary stenosis than those in the other group. From the perspective of gender analysis, homocysteine and apolipoprotein B significantly increased regardless of gender in severe coronary stenosis group. In men, the prevalence of diabetes rates and fasting plasma glucose were higher in severe coronary stenosis group. In women, the prevalence of triglyceride is obviously increased in severe coronary stenosis group. Male, smoking, homocysteine and apolipoprotein B were independent predictors of severe CAD in young and middle-aged patients according to logistic regression analysis with odds ratios of 2.798 (95% CI: 1.520~5.152; P<0.01), 3.570 (95% CI: 2.125~5.996; P<0.01), 1.079 (95% CI: 1.028~1.133; P<0.01), and 2.883 (95% CI: 1.427~5.825; P<0.01). Group analysis in the severe coronary stenosis patients revealed that only homocysteine was an independent predictor of LMA or proximal or mid-LAD lesion presence with an odds ratio of 0.911 (95% CI: 0.831~0.998; P<0.05). CONCLUSION: In our study, young and middle-aged patients with severe CAD have different risk profiles with higher frequency of male, smoking and increased levels of apolipoprotein B and homocysteine. Only homocysteine predicts coronary lesion distribution in LMA and proximal or mid-LAD.     

Relationship between levels of plasma endothelin-1/serum nitric oxide and hearing impairment in type 2 diabetes

AIM: To evaluate the relationship between endothelin-1 (ET-1)/nitric oxide (NO) and hearing impairment in type 2 diabetes mellitus (DM).METHODS: Eighty-eight type 2 diabetic patients with no signs of microangiopathy (retinopathy and nephropathy) or peripheral neuropathy, and 53 healthy subjects in the same period were enrolled in this study. Auditory function was evaluated using pure tone audiometry. Totally,type 2 DM group (n=88) and normal control group (NC, n=53) were divided into subgroups based on the presence and absence of hearing impairment. The concentration of plasma ET-1 was detected by radioimmunoassay. The concentration of serum NO was measured by the method of nitric acid reductase.RESULTS: Significantly increased plasma ET-1 and decreased serum NO were observed in diabetic patients with hearing impairment compared with those in diabetic patients without hearing impairment. The results of multivariate logistic regression analysis showed that hearing impairment in type 2 DM group was significantly associated with elevated level of HbA1c (OR＝4.525, P<0.05), LDL-C (OR=2.381,P<0.05) and plasma ET-1 (OR＝6.207,P<0.01). Besides, elevated serum level of NO (OR＝0.862, P<0.05) was associated with lower risk of hearing impairment in diabetics.CONCLUSION: Hearing impairment may happen earlier than other complications in diabetic patients. In addition to hyperglycemia and hyperlipemia, high level of ET-1 and low levels of NO might contribute to hearing impairment in diabetic patients.     

Pathophysiologic changes of local ischemic coronary artery and cardiac muscle after ligating canine LAD

AIM: To evaluate the reliability of making a research model of coronary artery stenosis and local myocardial infarction reproduced in dog by ligating canine LAD. METHODS: We disparted 30 aged healthy cross-breed dogs ［(18.5±6.7) kg］ into three groups. The near part of the LAD through left minimal thoracic incision was ligated to interdict 25% (group A), 50% (group B), 75% (group C) of the flux, respectively. The changes of plasma endothelium-derived factors NO, ET-1, sP-selectin and CTnT were measured before ligation and at different time points after ligation. The expression of P-selectin gene in cardiac muscle was detected by Western blotting. The segments of distal parts of the ligated LAD were cut and pathological changes of the patches of topical cardiac muscle were observed by electronic microscope. RESULTS: After ligation, NO/ET-1, P-selectin and CTnT had significant changes in group B (P<0.05) and group C (P<0.01). The expression of P-selectin of cardiac muscle was highly up-regulated after ligating in B (50%) and C (75%) group, In C group animals, a typical far more intense expression pattern was found. Under electronic microscope, the endothelium and other structures of the LAD wall and ultrastructure of myocardial cells had obvious changes in later two groups, especially in group C. There were a typical stenosis of LAD and myocardial infarction. CONCLUSIONS: Ligating the LAD 75% severely damages the endothelial cell and cardiac muscle cells of local ischemic vessel and cardiac muscle, thus forms the typical local stenosis of coronary artery and myocardial infarction, such method is a safe and reasonable way for making a disease model for studying CABG in surgery.     

Plasma circulating miR-126 in patients with coronary artery heart disease and its effect on vascular endothelial cells

AIM: To investigate the role of plasma circulating miR-126 and miR-16 in the patients with coronary artery heart disease and to explore the influence of miR-126 on vascular endothelial cells. METHODS: Plasma total RNA was isolated from 52 patients with stable coronary artery disease and 52 healthy volunteers. The circulating miR-126 and miR-16 in those people were detected using specific primers. Endothelial cell line EA.hy926 was transfected with a miR -126 inhibitor, and total RNA of the cells was isolated 30 h after transfection to detect the expression level of vascular endothelial growth factor (VEGF). RESULTS: The expression of plasma circulating miR-126 was significantly decreased in the patients with coronary artery heart disease compared with healthy controls (P<0.05). No significant difference of circulating miR-16 between the patients with coronary artery heart disease and healthy controls was observed (P>0.05). The expression of VEGF in the endothelial cell line EA.hy926 transfected with miR-126 inhibitor was 2.08 times higher than that in negative control cells 30 h after transfection (P<0.05). CONCLUSION: Plasma circulating miR-126 is significantly decreased in the patients with coronary artery heart disease. Plasma circulating miR-16 in the patients with coronary artery heart disease and in the healthy controls is stable. miR-126 negatively regulates the expression of VEGF in vascular endothelial cells.     

Effects of external counterpulsation on the hemodynamics and endothelin-1 in myocardial ischemia canines

AIM: To investigate the effects of external counterpulsation (ECP) on the hemodynamics indexes and endothelin-1 (ET-1) in myocardial ischemia canines. METHODS: Nineteen health dogs were randomly divided into controls, ischemia and ECP groups. The blood pressure, left ventricular systolic and diastolic pressure, +dp/dtmax and -dp/dtmax, brachiocephalic trunk blood flow were recorded. Plasma and myocardium ET-1levels were determined by radioimmunoassay. RESULTS: 60 minutes after left anterior descending of coronary artery ligation, compared with controls, the blood pressure decreased greatly, left ventricular systolic and diastolic function declined, brachiocephalic trunk blood flow reduced, but plasma ET-1 levels were increased significantly in ischemia and ECP groups (P<0.05). After 2 h ECP treatment, compared with ischemia, blood pressure increased, left ventricular systolic and diastolic function improved, brachiocephalic trunk blood flow raised, but the plasma and myocardium ET-1 levels were decreased in ECP group (P<0.05). CONCLUSION: The results suggest that ECP improves the hemodynamics indexes in myocardial ischemia canine, and ET-1 may play an important role.     

Association of coagulation factor Ⅻ gene C46T polymorphism and coronary artery disease in patients documented angiography

AIM: To study the distribution of C46T polymorphism of factor Ⅻ(FⅫ) in Chinese Han population and the association of the polymorphism with coronary artery disease(CAD) and acute coronary syndrome(ACS). METHODS: Selected coronary angiography was performed in 168 CAD patients and 210 controls. Genetype of FⅫ was typed by mutagenically separated polymerase chain reaction assay(MSPCR). RESULTS: FⅫ allelic frequencies of C and T were 29.8%, 70.2% and 31.4%, 68.6% in CAD and controls, respectively(P>0.05). Genetype distribution was in accordance with Hardy-Weinberg equilibrium. The frequency of CC, CT, TT in CAD and control was 8.7%, 40.5%, 50.0% and 5.2%, 52.6%, 42.2%. The association between FⅫ genetype and CAD(2=6.393, P<0.05) was observed. As compared with the CC group, the CT genetype was a protective factor for CAD(OR 0.43, 95% CI 0.19-0.97). When compared to stable coronary artery disease, the frequency of TT genetype is significant less in ACS group(45.0% vs 62.5%, 2=4.200, P<0.05). The distribution of genetype in C46T was no significant difference among the numbers of stenosed coronary artery. CONCLUSION: The C46T polymorphism of FⅫ is association with CAD in Chinese Han population. The C→T mutation may be a protective factor against CAD and ACS.     

Levels of CGRP and ET-1 in plasma of pulmonary artery and thoracic aorta and in the extractives of lung and ventricular tissues of the chronic hypoxic rats

AIM AND METHODS: To explore the effects calcitonin gene-related peptide (CGRP) and endothelin-1(ET-1) on the mechanisms of hypoxic pulmonary hypertension (HPH), the contents of CGRP and ET-1 in plasma of pulmonary artery and thoracic aorta and in extractives of lung and ventricular tissues of the chronic hypoxic rats were determined by radioimmunoassay. The changes of their hemodynamic indices and right heart hypertrophy index were monitored simultaneously. RESULTS: The level of pulmonary artery plasma CGRP was significantly higher than that of thoracic aorta plasma, but just the reverse was ET-1 or the ratio of ET-1 and CGRP in control rats( P<0.01). Compared with controls, the level of pulmonary artery plasma CGRP was gradually reduced in all hypoxic rats, but ET-1 was enhanced after 7 and 14 days of hypoxia and was decreased after 21 days of hypoxia. With prolonging time exposed to hypoxia, the level of thoracic aorta plasma CGRP was markedly increased in hypoxic animals compared with controls ( P<0.05), the positive correlation significantly with increased pulmonary arterial pressure( r = -0.896, P =0.05), but the lower level of thoracic aorta plasma ET-1 showed or negative correlation with pulmonary arterial pressure. CONCLUSIONS: These data suggest that the unbalance of effects of CGRP and ET may plays an important role in regulating the resistance of pulmonary circulation and has close relation with the formation of HPH.     

Effect of non-invasive ischemic preconditioning on nitric oxide/endothelin-1 imbalance and gas exchange impairment following limb ischemia reperfusion: a clinical study

AIM: To investigate the effects of non-invasive ischemic preconditioning on nitric oxide (NO)/endothelin-1 (ET-1) imbalance and gas exchange impairment following limb ischemia reperfusion in patients undergoing unilateral lower extremity surgery with tourniquet. METHODS: Twenty-seven patients aged 25-65 years, whose tourniquets duration varied from 1 h to 1.5 h and matched American Society of Anesthesiologists Physical Status Ⅰ-Ⅱ, were randomized into two groups: a control group (n=14) and a ischemic preconditioning group (IPC group, n=13) in which patients received three cycles of 5 min of ischemia/5 min of reperfusion before tourniquet inflation. Radial arterial blood gas, plasma malondialdehyde (MDA) and NO, serum ET-1 and interleukin-6 (IL-6) were measured just before tourniquet inflation(T0), 1 h after inflation(T1), and 0.5 h(T2), 2 h(T3), 6 h(T4), 24 h(T5) after tourniquet deflation. Meanwhile NO/ET-1 ratio, alveolar-arterial oxygen gradient (PA-aDO2) and intrapulmonary shunt (Qs/Qt) were calculated. RESULTS: In control group, arterial partial pressure of oxygen (PaO2) were decreased, while PA-aDO2 and Qs/Qt were increased significantly at T4 compared to the baselines at T0 (P<0.01). Plasma NO levels and NO/ET-1 ratios decreased gradually after tourniquets deflation and statistical significances were observed at T3 (P<0.01) with a valley at T4 (P<0.01) and recovered to baselines at T5. Serum ET-1, IL-6 and plasma MDA began to increase remarkably after T3 (P<0.05 or P<0.01), peaked at T4 and dropped slightly at T5. The changes above-mentioned could be well attenuated by the application of IPC (P<0.05 or P<0.01) except PaO2 (P>0.05). CONCLUSION: Clinical application of unilateral tourniquet within safe time limit (1.5 h) may lead to limb ischemia reperfusion and further pulmonary gas exchange impairment, which could be partially attenuated by the application of IPC via alleviating NO/ET-1 imbalance.     

Effects of She Xiang Bao Xin Wan (SXBXW) on the proliferation of primary cultured human umbilical artery vascular smooth muscle cells induced by endothelin-1

AIM: To observe the effects of She Xiang Bao Xin Wan (SXBXW) of Chinese patent medicine on the proliferation of primary cultured vascular smooth muscle cells (VSMCs) from human umbilical artery and stimulated by endothelin-1 (ET-1) in vitro. METHODS: The proliferation cell models of primary cultured VSMCs were established by ET-1 stimulation. Six groups in the experiment were divided into control group; ET-1 group; ET-1+SXBXW 0.25 g/L; ET-1+SXBXW 0.5 g/L; ET-1+SXBXW 1.0 g/L and ET-1+SXBXW 2.0 g/L groups, respectively. The proliferation induced by ET-1 and the suppression mediated by SXBXW on VSMCs were measured by MTT method. The inhibitory rate and the cytotoxicity of SXBXW were detected by lactate dehydrogenase colorimetry and trypan blue exclusion tests. The effect of ET-1 and SXBXW on the cell proliferation cycle was analyzed by flow cytometry. RESULTS: Compared to control group, ET-1 significantly enhanced the proliferation of VSMCs (P<0.01). However, a certain dose of SXBXW inhibited effectively the proliferation of VSMCs induced by ET-1 in a dose-dependent manner (P<0.01). Meanwhile, SXBXW showed no influenced on both the number of living cells and the release of lactate dehydrogenase, although it inhibited the proliferation of VSMCs, indicating that SXBXW was no cytotoxicitic effect on VSMCs. ET-1 enhanced the proliferation of VSMCs by means of promoting the transition of the cell cycle from G1 phase to S phase. However SXBXW significantly inhibited the proliferation mediated by ET-1. CONCLUSION: SXBXW plays the role in suppressing VSMCs proliferation induced by ET-1. The mechanism may be involved in blocking the cell cycle from G1 phase into S phase.     

Mitral annulus velocities and time intervals for evaluation of global left ventricular diastolic function in patients with coronary artery disease

AIM: To detect and compare the longitudinal mitral annulus diastolic velocity and time interval changes by pulsed Doppler tissue imaging (DTI) in patients with angina pectoris (AP) and myocardial infarction (MI), and to explore the value of mitral annulus diastolic velocities and time intervals for evaluation of global left ventricular diastolic dysfunction. METHODS: Fifty patients with established coronary artery disease were divided into AP group (16 cases) and MI group (34 cases). Sixteen age-matched healthy individuals served as the control group. The septum, lateral, anterior and inferior walls of the mitral annulus were displayed, and selected for DTI spectrum sampling. Peak early and late diastolic velocities and their ratio, time to the onset and peak of the early diastolic wave, and regional isovolumic relaxation time were measured, and the average values of the four mitral annular sites were calculated and presented as Em, Am, Em/Am, QEm, TEm and IVRTm, respectively. RESULTS: Compared with the control group, Em and Em/Am were significantly lower in both the AP and the MI groups (P<0.01). Em was even lower in the MI group than that in the AP group (P<0.01). QEm, TEm and IVRTm were significantly longer in the AP and the MI groups than those in control group (P<0.01 or P<0.05). IVRTm was even longer in the MI group than that in AP group (P<0.01). IVRTm had significantly negative correlation with Em (r=-0.64, P<0.01). CONCLUSION: Em, Em/Am, QEm, TEm and IVRTm as measured by pulsed DTI may be promising indexes for quantitative assessment of global left ventricular diastolic dysfunction in patients with coronary artery disease. Em and IVRTm may indicate the severity of ischemic myocardial damage.     

Effects of atorvastatin on nitric oxide,endothelin-1 and myocardial function in a rabbit model of acute myocardial infarction and reperfusion

AIM: To evaluate the effects of atorvastatin on nitric oxide(NO), endothelin-1(ET-1)and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion(AMI/R). METHODS: Twenty-four rabbits were randomized into 3 groups: 8 in AMI/R group, 8 in atorvastatin-treated group(5 mg·kg-1·d-1)and 8 in sham-operated group. Animals in the former two groups were subjected to 60 min of coronary occlusion followed by 120 min of reperfusion. Data on haemodynamics were collected. NO in blood sample, and in normal, and in infarcted reflow and no-reflow myocardium were evaluated respectively by nitrate reductase method. The levels of ET-1 in blood sample, and in normal, infarcted reflow and no-reflow myocardium were determined by radioimmunoassay. RESULTS: (1)Compared to the baselines, the heart rate(HR), systolic blood pressure(SBP), diastolic blood pressure(DBP), left ventricular systolic pressure(LVSP), maximal rate of increase and decline in left ventricular pressure(±dp/dtmax)and cardiac output(CO)in AMI/R and atorvastatin-treated groups were significantly declined, whereas left ventricular end-diastolic pressure(LVEDP)was increased after 60 min of coronary occlusion and 120 min of reperfusion(P<0.05 or P<0.01). However, in atorvastatin-treated group, LVSP, LVEDP, ±dp/dtmax and CO at the time point of 120 min of reperfusion recovered more significantly than those at the time point of 60 min of coronary occlusion(P<0.01), which was more significant than those in AMI/R group(P<0.05 or P<0.01). Compared to AMI/R group, the SBP and DBP were significantly heigher in atorvastatin-treated group(P<0.01).(2)In atorvastatin-treated group, the levels of ET-1 in blood sample were significantly lower than those in AMI/R group(P<0.01), and the levels of NO were significantly higher(P<0.01). Moreover, the levels of NO or ET-1 in infarcted reflow myocardium were significantly lower than that in AMI/R group(P<0.05 or P<0.01).(3)Atorvastatin could ameliorate myocardial function. CONCLUSION: Atorvastatin is effective in increasing NO and reducing ET-1 in blood plasma and local myocardium, and in protection of endothelial cells. Atorvastatin also has a beneficial effect on improving left ventricular function during acute myocardial infarction and reperfusion in rabbits.     

Association between plasma level of microRNA-21 and pulmonary hypertension in heart failure patients with preserved ejection fraction

AIM: To investigate the correlation between microRNA-21 (miR-21) and pulmonary hypertension(PH) in the patients with heart failure with preserved ejection fraction (HFpEF). METHODS: From January 2014 to February 2016, 102 HFpEF patients presenting to Jiangxi Provincial People's Hospital were enrolled in this study. The patients were divided into PH-HFPEF group (n=36, PASP ≥ 50 mmHg) and HFpEF group (n=40, PASP<50 mmHg). Another 36 age-and sex-matched subjects served as healthy controls. The plasma level of miR-21 and its correlations with clinic data were examined, and multivariate logistic regression analysis was performed to identify the independent predictors of PH-HFpEF. Receiver operating characteristic (ROC) curve was analyzed, and the area under the curve (AUC) was calculated. The sensitivity and specificity for PH-HFPEF diagnosis were also determined. RESULTS: Age, plasma endothelin-1 (ET-1), interleukin-6 (IL-6), brain natriuretic peptide (BNP) and left atrial diameter (LAD) were significantly higher in PH-HFPEF group than those in HFPEF group (P<0.05). The level of miR-21 was significantly increased in PH-HFPEF group compared with HFpEF group and healthy control group. In addition, the miR-21 level was correlated with PASP (r=0.267, P=0.000), plasma IL-6 (r=0.302, P=0.013) and left ventricular mass index (LVMI) (r=0.515, P=0.036). Plasma IL-6 was positively correlated with plasma ET-1 (r=0.622, P=0.002). PASP was positively correlated with plasma IL-6 (r=0.36, P=0.023), ET-1 (r=0.76, P=0.004), BNP (r=0.43,P=0.031), and LAD (r=0.39, P=0.044). ROC curve showed that the AUC of miR-21 was 0.80. Multivariate logistic regression analysis showed that miR-21, LAD and BNP were the independent predictors of PH-HFpEF. CONCLUSION: Increased plasma miR-21 level is positively correlated to PH-HFpEF, and is an independent predictor of PH-HFpEF, suggesting that plasma miR-21 might be a useful new biomarker for predicting PH in HFpEF patients.     

Endothelin-1 and eNOS expression in pulmonary aterioles of patients with congenital heart diseases with pulmonary hypertension

AIM: To clarify the role of eNOS and ET-1 in development of pulmonary hypertension (PH) associated with congenital heart diseases. METHODS: 40 patients were randomly divided into three groups: severe or moderate PH group (group A, 12 cases), slight PH group (group B, 14 cases) and normal group (group C, 14 cases). ET-1 and eNOS were examined by using the technique of immunohistochemistry. RESULTS: ① Plasma ET-1 concentration was significantly higher in group A and B than that in group C (P<0.01). Serum NO concentration in group A and B was significantly lower than that in group C (P<0.01). ② The proliferation of medial smooth muscle cells and collagenous fibers of pulmonary arteriole in patients with PH were observed by electron microscopy. ③ ET-1 in pulmonary arteriole was significantly higher in group A and group B than that in group C (P<0.01). eNOS in pulmonary arteriole was significantly lower in group A and group B than that in group C (P<0.01). CONCLUSION: ET-1 and eNOS may play an important role in the pathogenesis of PH.     

Influence of chronic stress on vasoactive substances and inflammatory factor in rat model with acute myocardial infarction by factorial analysis

AIM: To investigate the effect of chronic unpredictable mild stress(CUMS) on plasma endothelin, nitric oxide and interleukin-6, high-sensitivity C-reactive protein(hs-CRP) in rats after acute myocardial infarction(AMI).METHODS: After the rats of myocardial infarction(MI) were established, the animals were treated under the condition of CUMS for 4 weeks, then the contents of plasma(or serum) endothelin, nitric oxide, interleukin-6 and hs-CRP were measured and data were analyzed by two factor factorial analysis. RESULTS: The results of factorial analysis showed: MI alone had no significantly effect on the level of nitric oxide(P>0.05), but CUMS had significantly effect on increasing the level of nitric oxide(P<0.01). The CUMS had significantly interaction with MI on increasing the level of nitric oxide(P<0.01). Both MI and CUMS increased the level of hs-CRP(all P<0.01). However, no interaction was discovered between MI and CUMS(P>0.05). Both MI and CUMS had no effect on the level of ET-1 and IL-6(P>0.05).CONCLUSION: CUMS increases nitric oxide content and has cooperative effect with MI on increasing NO, both MI and CUMS significantly increase the level of CRP, but have no effect on the level of ET-1 or IL-6, suggesting that the abnormal increase in nitric oxide and hs-CRP contents may be the important pathophysiological changes of post-MI depression.     

Effect of tongxinluo capsule on endothelial function in stable angina pectoris patients

AIM:To investigate clinical effect of tongxinluo capsule in treating stable angina pectoris patients,and its influence on endothelial function,superoxide dismutase (SOD) and malondialdehyde (MDA).METHODS:One hundred and twenty-four stable angina pectoris patients were divided into three groups,isosorbide treatment group (41 cases),tongxinluo capsule treatment group (40 cases),tongxinluo and isosorbide treatment group (combined treatment group,43 cases).The serum concentrations of nitric oxide (NO),endothelin-1 (ET-1),SOD and MDA were determined before and after treatment.The data in traetment groups were compared with that in normal control.RESULTS:The symptoms of 3 groups were significantly improved,and the total effective rate of tongxinluo capsule group and combined treatment groups were better than that in isororbide treatment group (85.00% and 88.37% vs 73.17%,P<0.05).Before treatment,the levels of serum NO and activity of SOD in angina patients were lower than that in control group.The serum MDA and ET-1 levels were higher than those in control.The levels of serum NO and SOD activity were increased remarkably after tongxinluo capsule or tongxinluo combined treatment.However,besides the concentration of NO increased after isosorbide treatment,the levels of serum ET-1 and MDA and SOD activity were not changed.CONCLUSIONS:The results suggest that tongxinluo capsule could effectively improve the symptoms of stable angina pectoris,and it is important for tongxinluo capsule to increase NO level and decrease ET-1 product,scavenge free radical and prevent lipid peroxidation.     

Studies on the role of ET-1 and CGRP in the pathophysiology of ankylosing spondylitis and rheumatoid arthritis

AIM: To clarify the role of endothelin-1 (ET-1) and calcitonin gene related peptide(CGRP) in the pathophysiology of ankylosing spondylitis and rheumatoid arthritis. METHOD: Plasma/synovial fluid ET-1 and CGRP were measured by radioimmunoassay in patients with ankylosing spondylitis (AS) or rheumatoid arthritis (RA) and healthy control. RESULTS: ET-1 level in plasma of patients with AS and RA were significantly higher than that of healthy controls (P<0.01). No difference was found in plasma CGRP level between AS or RA and healthy control (P>0.05). CGRP level in synovial fluid was significantly higher than that in plasma (P<0.01), but ET-1 level was significantly lower than in plasma (P<0.01). CONCLUSION: These results suggest that ET-1 and CGRP play a pathogenic role in AS and RA.