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ABSTRACT: Although microRNAs (miRNAs) have been intensively studied in cardiac fibrosis, their roles in drug-mediated anti-fibrotic therapy are still unknown. Previously, Pioglitazone attenuated cardiac fibrosis and increased miR-711 experimentally. We aimed to explore the role and mechanism of miR-711 in pioglitazone-treated myocardial infarction in rats. Our results showed that pioglitazone significantly reduced collagen-I levels and increased miR-711 expression in myocardial infarction heart. Pioglitazone increased the expression of miR-711 in cardiac fibroblasts, and overexpression of miR-711 suppressed collagen-I levels in angiotensin II (Ang II)-treated or untreated cells. Transfection with antagomir-711 correspondingly abolished the pioglitazone-induced reduction in collagen-I levels. Bioinformatics analysis identified SP1, which directly promotes collagen-I synthesis, as the putative target of miR-711. This was confirmed by luciferase assay and western blot analysis. Additionally, increased SP1 expression was attenuated by pioglitazone in myocardial infarction heart. Furthermore, transfection of antagomir-711 attenuated pioglitazone-reduced SP1 expression in cardiac fibroblasts with or without Ang II stimulation. We conclude that pioglitazone up-regulated miR-711 to reduce collagen-I levels in rats with myocardial infarction. The miR-711-SP1-collagen-I pathway may be involved in the anti-fibrotic effects of pioglitazone. Our findings may provide new strategies for miRNA-based anti-fibrotic drug research.
Science China. Life sciences 05/2013; 56(5):431-9. · 2.02 Impact Factor
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ABSTRACT: Coronary artery disease is the leading cause of death in China. Percutaneous coronary intervention is a recent milestone technology for treatment coronary artery disease. However, clinical decision making for patients with intermediate coronary stenosis is still controversial. We designed this study to assess the optimal intravascular ultrasound (IVUS) criteria for predicting functional significance of intermediate coronary lesions.
We enrolled 141 patients with 165 intermediate coronary lesions located in vessels with a diameter ≥ 2.50 mm. IVUS of intermediate coronary lesions were performed before intervention. Pressure-derived fractional flow reserve (FFR) was measured at maximal hyperemia induced by adenosine infusion. An FFR < 0.80 was considered as abnormal functional significance.
For the overall 165 lesions, the mean FFR value was 0.84 ± 0.09. The diameter of the stenosis by visual estimation on angiogram was (59.63 ± 11.29)%. Minimum lumen diameter (MLD), minimum lumen area (MLA) and plaque burden (PB) were (2.00 ± 0.36) mm, (3.88 ± 1.34) mm(2), (67.28 ± 9.89)% respectively by IVUS measurements. An FFR < 0.80 was seen in 43 lesions (30.5%). There was a moderate correlation between IVUS parameters and FFR, including MLD (r = 0.372, P < 0.001), MLA (r = 0.442, P < 0.001) and PB (r = -0.172, P < 0.05). MLA was a predictor for FFR as a continuous variable independent of possible confounding variables (P < 0.05), and MLA and PB, were predictors for FFR < 0.80 as binary variables (P < 0.05). The best cutoff value of MLA to predict FFR < 0.80 was < 3.15 mm(2), with a 73.6% diagnostic accuracy; sensitivity 71.4%, specificity 67.0%, AUC = 0.709, and P < 0.001. The cutoff value of the PB to predict FFR < 0.80 was 65.45%; sensitivity 82.6%, specificity 41.2%, AUC = 0.644, and P < 0.01. If both MLA and PB were taken into account, the negative predictive value and the positive predictive value were 88.7% and 64.8% respectively.
Anatomic measurements of intermediate coronary lesions obtained by IVUS showed a moderate correlation to FFR values. IVUS-derived MLA ≥ 3.15 mm(2) may be useful to exclude FFR < 0.80, but poor specificity limits its applicability for physiological assessment of lesions < 3.15 mm(2). MLA was one of many factors affecting coronary flow hemodynamics. Both MLA and PB should be taken into account when determining functional ischemia.
Chinese medical journal 05/2013; 126(9):1606-11. · 0.86 Impact Factor
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ABSTRACT: BACKGROUND: Impaired coronary flow reserve (CFR) in patients with hypertension may be caused by epicardial coronary stenosis or microvascular dysfunction. Antihypertensive treatment has been shown to improve coronary microvascular dysfunction. The aim of this study was to evaluate the impact of uncontrolled blood pressure (BP) on diagnostic accuracy of CFR for detecting significant coronary stenosis. METHODS: A total of 98 hypertensive patients scheduled for coronary angiography (CAG) due to chest pain were studied. Of them, 45 patients had uncontrolled BP (defined as the office BP ≥ 140/90 mmHg (1 mmHg = 0.133 kPa) in general hypertensive patients, or ≥ 130/80 mmHg in hypertensive individuals with diabetes mellitus), and the remaining 53 patients had well-controlled BP. CFR was measured in the left anterior descending coronary artery (LAD) during adenosine triphosphate-induced hyperemia by non-invasive transthoracic Doppler echocardiography (TTDE) within 48 hours prior to CAG. Significant LAD stenosis was defined as > 70% luminal narrowing. Diagnostic accuracy of CFR for detecting significant coronary stenosis was analyzed with a receiver operating characteristic analysis. RESULTS: CFR was significantly lower in patients with uncontrolled BP than in those with well-controlled BP (2.1 ± 0.6 vs. 2.6 ± 0.9, P < 0.01). Multivariate linear regression analysis of the study showed that the value of CFR was independently associated with the angiographically determined degree of LAD stenosis (β = -0.445, P < 0.0001) and the presence of uncontrolled BP (β = -0.272, P = 0.014). With a receiver operating characteristic analysis, CFR < 2.2 was the optimal cut-off value for detecting LAD stenosis in all hypertensive patients (AUC 0.83, 95%CI 0.75 - 0.91) with a sensitivity of 75%, a specificity of 78%, and an accuracy of 77%. A significant reduction of diagnostic specificity was observed in patients with uncontrolled BP compared with those with well-controlled BP (67% vs. 93%, P = 0.031). CONCLUSIONS: CFR measurement by TTDE is valuable in the diagnosis of significant coronary stenosis in hypertensive patients. However, the diagnostic specificity is reduced in patients with uncontrolled BP.
Chinese medical journal 03/2013; 126(5):839-844. · 0.86 Impact Factor
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ABSTRACT: BACKGROUND: As an adipocytokine, resistin has been proposed as a link between inflammation, metabolic disorder and atherosclerosis. The aim of the study is to evaluate whether serum resistin is associated with acute coronary syndrome (ACS) and major adverse cardiovascular events (MACEs) among postmenopausal women with ACS undergoing percutaneous coronary intervention (PCI). METHODS: A total of 106 consecutive postmenopausal women who underwent coronary angiography for evaluation of suspected myocardial ischemia were enrolled. Pre-procedure serum resistin, inflammatory and metabolic biomarkers were measured. All participants were followed for seven years for MACEs, including cardiovascular death, recurrent nonfatal myocardial infarction, and re-PCI. RESULTS: Patients with ACS (n = 69) had significantly higher resistin levels than those without coronary artery disease (CAD) (n = 37) (4.61 (1.79 - 10.80) ng/ml vs. 2.36 (0.85 - 4.15) ng/ml, P = 0.002). Correlation analysis revealed positive correlations between resistin levels and inflammatory and metabolic factors (P < 0.05). A follow-up of a mean of 83.4 months showed that patients with ACS suffered more MACEs than those without (13.0% vs. 2.7%, P = 0.05). Adjusted for cardiovascular risks, inflammatory and metabolic factors, multiple Logistic regression analysis indicated that an elevated resistin level was an independent predictor of ACS onset (OR = 1.139, 95%CI 1.024 - 1.268, P = 0.017) and of MACEs after PCI (OR = 1.099, 95%CI 1.015 - 1.189, P = 0.019). To clarify the association between resistin levels and MACEs, ACS patients were divided into two subgroups on the basis of resistin levels. Compared with the low resistin subgroup (≤ 4.35 ng/ml, n = 32), patients in the high resistin subgroup (> 4.35 ng/ml, n = 37) were more prone to suffer MACEs (21.6% vs. 3.1%, P = 0.015). Kaplan-Meier analysis showed a significantly lower event-free survival rate in ACS patients with high resistin levels than in the low resistin subgroup (78.4% vs. 96.9%, Log rank 5.594, P = 0.018). CONCLUSION: An elevated serum resistin level is associated with ACS and cardiovascular events and acts as a predictor in progression of ACS in postmenopausal women.
Chinese medical journal 03/2013; 126(6):1058-1062. · 0.86 Impact Factor
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ABSTRACT: To assess the diagnostic accuracy of coronary flow reserve measured by transthoracic Doppler echocardiography (TTDE) associated with adenosine triphosphate (ATP) stress for detecting coronary stenosis in patients with chest pain.
A total of 125 patients scheduled for elective coronary angiography (CAG) due to chest pain were recruited. ATP stress echocardiography were performed to measure CFR in left anterior descending (LAD) by TTDE with 2 days pre-CAG. Coronary flow reserve (CFR) was calculated as peak diastolic velocity during maximum hyperemia (PDV2) divided by baseline (PDV1). According to the coronary angiography results, all patients were divided into group A (stenosis < 50% in LAD, n = 57), group B (stenosis of 50% - 75% in LAD, n = 20) and group C (stenosis > 75% in LAD, n = 48). Then CFR was compared among three groups. The receiver operating characteristic curve (ROC) was used to assess the value of CFR for detecting LAD stenosis.
CFR was significantly different among three groups (group A: 3.02 ± 0.85, group B: 2.49 ± 0.65, group C: 1.82 ± 0.56; all P < 0.01). With ROC analysis, CFR < 2.2 was the best cut-off value for diagnosing significant LAD stenosis (area under curve: 0.86 (95% CI 0.80 to 0.93)), with sensitivity of 81%, specificity of 83% and accuracy of 82%; CFR < 2.2 for diagnosing LAD stenosis > 50% (area under curve: 0.81 (95%CI 0.74 - 0.89, P < 0.01)), with a sensitivity of 59%, a specificity of 82% and an accuracy of 70%.
CFR measured by TTDE associated with ATP stress is a valuable tool for screening significant stenosis in patients with chest pain. Its advantages are non-invasiveness, easy availability, safety and inexpensiveness.
Zhonghua yi xue za zhi 02/2013; 93(6):432-5.
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ABSTRACT: Despite outstanding antiplatelet properties of aspirin and clopidogrel, some patients taking these drugs continue to suffer complications. Antiplatelet resistance appears to be a new prognostic factor in acute coronary syndrome patients for clinical events associated with stent thrombosis (ST). However, there is no optimal method to identify it and assess its correlation to clinical outcomes. This study sought to evaluate the predictive value of antiplatelet resistance assessed by whole blood impedance aggregometry for the risk of early ST in patients with acute coronary syndrome who underwent coronary stenting.
Platelet responses to aspirin and clopidogrel in 86 patients with acute coronary syndrome were measured by whole blood impedance aggregometry. Spontaneous platelet aggregation was defined as antiplatelet resistance identified by the increased electrical impedance. The clinical endpoint was early stent thrombosis during 30-day follow-up after coronary stenting.
The prevalence of aspirin resistance, clopidogrel resistance and dual resistance of combined clopidogrel and aspirin resistance were 19.8%, 12.8% and 5.8% respectively. Diabetes, female and higher platelet counts were more frequently detected in clopidogrel-resistant and dual-resistant patients. During 30-day follow-up, the patients with clopidogrel resistance and dual resistance had higher incidence of early stent thrombosis (18.2% vs. 1.3%, 40.0% vs. 1.2%, P < 0.05). Binary Logistic Regression analysis indicated that dual resistance remained an independent predicator for early stent thrombosis (odds ratio 34.064, 95%CI 1.919 - 604.656, P = 0.016).
Antiplatelet resistance assessed by whole blood impedance aggregometry is paralleled to clinical events, and dual antiplatelet resistance is an independent predicator for early stent thrombosis in patients with acute coronary syndrome. As a physiological assessment of platelet reactivity, whole blood impedance aggregometry is a convenient and accurate option for measuring antiplatelet resistance and hence predicting early stent thrombosis.
Chinese medical journal 02/2013; 126(4):626-33. · 0.86 Impact Factor
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ABSTRACT: To investigate the correlation between left atrial size and left ventricular filling pressure (LVFP) and the value of left atrial size assessment on detecting diastolic dysfunction in hypertensive patients with preserved LVEF by echocardiography.
Echocardiography was performed in 346 hypertensive patients with preserved LVEF(≥ 50%), left atrial size including left atrial diameter (LAD) and left atrial area (LAA) was measured and indexed to body surface area (LADI, LAAI). The ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/Em) was determined and LVFP was calculated with the formula: LVFP = 1.24×E/Em + 1.9. Patients were divided into diastolic dysfunction group [DD group, LVFP > 15 mm Hg (1 mm Hg = 0.133 kPa), n = 81] and normal diastolic function group (NDF group, LVFP ≤ 15 mm Hg, n = 265).
As compared to patients in NDF group, the patients in DD group had larger LA [LADI: (21.4 ± 2.6) mm/m(2) vs. (19.6 ± 2.4) mm/m(2); LAAI: (12.1 ± 2.6) cm(2)/m(2) vs. (10.4 ± 1.7)cm(2)/m(2); all P < 0.01]. LA size parameters were positively correlated with LVFP (r = 0.211-0.450, all P < 0.01), LAAI was best correlated with LVFP (r = 0.450, P < 0.01). ROC analysis showed that LAAI ≥ 11.4 cm(2)/m(2) diagnosed DD with a sensitivity of 63%, specificity of 74% and accuracy of 72%.
Left atrium dilation correlates positively with LVFP in hypertensive patients with preserved LVEF. The LAAI is a more accurate parameter for identifying patients with diastolic dysfunction in this cohort.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 01/2013; 41(1):33-7.
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ABSTRACT: Coronary heart disease (CHD) is characterized by inflammatory process and endothelial dysfunction. To investigate angiopoietin-2 (Ang-2) profiles, we evaluated serum Ang-2 levels in different types of CHD in 166 subjects. Ang-2 was measured by enzyme-linked immunosorbent assay. Serum Ang-2 levels were significantly elevated in patients with CHD and gradually increased with advance of CHD. Ang-2 was positively correlated with Gensini scores and hs-CRP. Ang-2 might have potential implication in detecting and monitoring the progression of CHD.
Biomarkers 12/2012; 17(8):745-9. · 2.21 Impact Factor
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ABSTRACT: OBJECTIVE: To explore the relationship between early heart function impairment and exercise tolerance in patients with acute ST-elevation myocardial infarction (STEMI) and normal left ventricular ejection fraction (LVEF). METHODS: A total of 229 patients with a LVEF of ≥ 50% were retrospectively reviewed. There were 199 males and 30 females with a mean age of 56.2 ± 11.1 years. They underwent cardiopulmonary exercise testing (CPET) early after STEMI in a single exercise laboratory. Demographic data, presence of concomitant diseases, characteristics of STEMI, echocardiography and CPET findings were evaluated. RESULTS: Their mean LVEF was 60.2% ± 6.9% and the values of Vo(2peak) and Vo(2AT) were (21.8 ± 5.7) ml×kg(-1)×min(-1) and (19.4 ± 4.8) ml×kg(-1)×min(-1) respectively. Peak oxygen uptake (Vo(2peak)) showed a positive correlation with LVEF (r = 0.17, P = 0.012), E/A (r = 0.15, P = 0.033) and peak myocardial systolic velocity (Sm) (r = 0.30, P < 0.001). On the contrary, it varied inversely with peak A wave velocity (A) (r = -0.20, P = 0.005), E/Em (r = -0.16, P = 0.022) and left atrial pressure (LAP) (r = -0.16, P = 0.021). And there was a similar correlation between oxygen uptake at anaerobic threshold (Vo(2AT)) and LAP (r = -0.17, P = 0.031). After adjustments of subject demographic features and cardiovascular risk factors, Vo(2peak) was still associated with LVEF (β = 0.149, s = 0.051, sβ = 0.178, 95%CI 0.048 - 0.250, P = 0.004) and Sm (β = 0.606, s = 0.167, sβ = 0.245, 95%CI 0.277 - 0.936, P < 0.001). So did the relationship between Vo(2AT) and LAP (β = -0.271, s = 0.117, sβ = -0.172, 95%CI -0.501 - -0.040, P = 0.022). CONCLUSION: The exercise tolerance may be affected by early heart function impairment in STEMI patients. CPET is a sensitive detection tool of decreased heart function.
Zhonghua yi xue za zhi 11/2012; 92(42):2972-2975.
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ABSTRACT: To evaluate the predictive value of antiplatelet resistance assessed by whole blood electronic impedance aggregometry (EIA) for the risk of recurrent cardiac ischemic events in patients with acute myocardial infarction (AMI) who underwent coronary stenting.
We enrolled 109 patients with AMI, 72 (66.1%) men and 37 (33.9%) women with mean age (63 ± 12) years, who were treated with aspirin and clopidogrel daily after coronary stenting. EIA used arachidonic acid (AA) and adenosine diphosphate (ADP) as inductors to measure platelet aggregation inhibited by aspirin and clopidogrel respectively. The subjects were divided into four groups: pure aspirin resistant group (AR, electrical impedance > 0 Ω), pure clopidogrel resistant group (CR, electrical impedance ≥ 10 Ω), dual resistant group (DR) and dual sensitive group (DS). The primary outcomes were recurrent cardiac ischemic events during the 12-month follow-up.
Antiplatelet resistance occurred more often in patients with type 2 diabetes (P = 0.027). The platelet counts (PLT) were higher in antiplatelet resistant groups than DS group (P = 0.013). During the 12-month follow-up, the antiplatelet resistant patients had a higher incidence of recurrent cardiac ischemic events and stent thrombosis (ST) than the patients without (12.5%, 10.0%, 50.0% vs 3.8%, P = 0.036; 6.3%, 10.0%, 50.0% vs 1.3%, P = 0.000; respectively). Binary Logistic regression indicated that dual resistance remained an independent predicator of recurrence cardiac ischemic events and ST (OR 5.99, 95%CI 1.05 - 34.34, P = 0.045; OR 6.36, 95%CI 1.13 - 35.78, P = 0.036; respectively).
As a physiological assessment of platelet reactivity, EIA is a convenient and accurate option for measuring aspirin resistance. Antiplatelet resistance assessed by EIA is paralleled to clinical events. Dual resistance is an independent predicator for ST and recurrence cardiac ischemic events in patients with AMI.
Zhonghua yi xue za zhi 10/2012; 92(38):2677-80.
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Li-Jie Sun,
Lin Mi,
Ming Cui,
Li-Jun Guo,
Yong-Zhen Zhang,
Fu-Chun Zhang,
Jie Niu,
Hai-Yan Li,
Gui-Song Wang,
Jiang-Li Han, Wei Gao,
Dan Li,
Cui-Ping Li
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ABSTRACT: OBJECTIVE: To explore the relationship between quantitative coronary angiography (QCA) parameters and fractional flow reserve (FFR) for identifying ideal angiographic parameters predictive of myocardial ischemia. METHODS: The study included 121 lesions with QCA and FFR data from 106 patients [mean age: (63 ± 10) years]. The lesions were grouped into FFR > 0.75 group and FFR ≤ 0.75 group. Assessed parameters by QCA included percentage diameter stenosis, minimum luminal diameter (MLD), percentage area stenosis, minimum luminal area (MLA), reference vessel diameter (RVD) and lesion length (LL). Correlation analysis was used to identify the relationship between QCA parameters and FFR value, and receiver operating characteristic (ROC) curve was used to determine parameters predictive of FFR ≤ 0.75. RESULTS: LL was significantly higher [(14.8 ± 7.9) mm vs. (10.7 ± 5.4) mm, P = 0.024] while MLD [(1.47 ± 0.31) mm vs. (1.82 ± 0.51) mm, P = 0.028], RVD [(2.30 ± 0.50) mm vs. (2.81 ± 0.64) mm, P = 0.036], and MLA [(2.30 ± 1.50) mm(2) vs. (3.60 ± 2.30) mm(2), P = 0.038] were significantly lower in FFR ≤ 0.75 group than in FFR > 0.75 group. LL (r = -0.209, P = 0.040) was negatively correlated with FFR, and MLD (r = 0.414, P = 0.040), RVD (r = 0.303, P = 0.000) and MLA (r = 0.315, P = 0.002) were positively correlated with FFR. ROC analysis showed that MLD ≥ 1.6 mm was the best cut-off value to predict FFR > 0.75 with sensitivity 63%, specificity 82%, and positive predictive value 96%. CONCLUSIONS: QCA derived anatomic parameters of intermediate coronary lesions correlate to FFR value in some extent. MLD ≥ 1.6 mm is the best cut-off value to predict FFR > 0.75 in patients with intermediate coronary lesions.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 09/2012; 40(9):742-746.
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ABSTRACT: To analyze the relationship between serum total bilirubin coincident with congestive heart failure (CHF) exacerbation and subsequent long-term mortality in patients with CHF.
The study population consisted of 140 consecutive patients admitted for CHF exacerbation with left ventricular ejection fraction ≤ 45%. They were divided into 2 groups according to whether death attacked or not in the following 28.5 months. Binary logistic regression analysis was used to investigate independent predictors of death from clinical parameters on admission or within 24 hours.
Serum TBil and B-type natriuretic peptide (BNP) levels on admission were independent predictors of subsequent death after hospital discharge. According to increasing textiles of TBil stratified by the level of 12.8 and 18.2 mmol/L, the patients were divided into 3 groups: lower-level group (TBil ≤ 12.8 mmol/L), moderate-level group(TBil > 12.8 ∼ 18.2 mmol/L) and higher-level group (TBil > 18.2 mmol/L), with the death rates after 28.5 months of 12.2%, 17.9% and 38.9%, respectively(P = 0.002). Meanwhile, the pulse pressure decreased to (55.5 ± 17.3) mm Hg (1 mm Hg = 0.133 kPa), (48.9 ± 13.1) mm Hg and (46.1 ± 13.7) mm Hg, respectively (P = 0.008). TBil on admission had significant correlation with echocardiography-measured left ventricular endo-diastolic diameter (r = 0.34, P = 0.000) and right ventricular diastolic diameter (r = 0.23, P = 0.011).
Increased TBil coincident with cardiac decompensation predicts a worse long-term death of CHF, presumably through the potential liability to both decompensated RV function and lower cardiac output syndrome occurred simultaneously when HF deteriorates.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 09/2012; 51(9):677-9.
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Lei Song,
Yue-Jin Yang,
Shu-Zheng Lü,
Xin-Chun Yang,
Hong-Wei Li,
Jin-Cheng Guo, Wei Gao,
Chao-Lian Huang,
Quan Fang,
Ming-Ying Wu,
Heng-Jian Hao
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ABSTRACT: To analyze the cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) in Beijing area to evoke better individualized preventive approach.
In-hospital mortality and causes were analyzed based on database from Beijing percutaneous coronary intervention registry study (BJPCI Registry) in 2010.
A total of 4660 PPCI patients from 48 hospitals were included. In-hospital mortality was 2.4% (n = 110). Cardiogenic shock (39.1%, 43/110), mechanical complications (28.2%, 31/110) and intervention-related complications [28.2%, 31/110: procedure related (n = 28), drug related (n = 3)] were the leading causes of in-hospital death. Five deaths was attributed to comorbidity related reason (4.5%, 5/110). The in-hospital mortality had no significant difference among hospitals of different grade or total annual PCI (all P > 0.05). In-hospital mortality was slightly higher in hospital with annual PPCI < 300 than in hospitals with annual PPCI ≥ 300 (2.9% vs. 1.8%, P < 0.05).
Cardiogenic shock, mechanical complications and intervention-related complications are the main causes of in-hospital death among acute myocardial infarction patients receiving PPCI.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 07/2012; 40(7):554-9.
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ABSTRACT: Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.
Endocrinology 06/2012; 153(8):3692-700. · 4.46 Impact Factor
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ABSTRACT: To investigate the relationship between regular exercise habit and peak oxygen uptake (VO₂peak) early after acute ST-elevation myocardial infarction (STEMI).
A total of 239 patients who underwent cardiopulmonary exercise testing (CPET) early after STEMI in a single exercise laboratory were enrolled. Influencing factors to VO₂peak were analyzed retrospectively.
There were 53.6% patients reported to have regular exercise habits before STEMI. No significant difference between patients with and without exercise habit in VO(2)peak early after STEMI (P = 0.317) were found by t test. After adjusted by risk factors including demographic features, clinical characteristics and cardiovascular, etc, regular exercise habit was an independent factor for VO₂peak (β = 1.703, P = 0.015). Following age-stratification, the significant difference was found between patients with and without exercise habits in VO₂peak only in patients aged between 40 - 49 years old (P = 0.004).
The relationship between regular exercise habit and VO₂peak early after STEMI suggests that exercise tolerance of patients with exercise habit will be better than sedentary patients even after STEMI, in particular to patients aged between 40 - 49 years old.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 06/2012; 51(6):453-5.
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ABSTRACT: To dynamically observe how glioma stem cells promote the tumor formation and angiogenesis, and to study the correlation between the distribution of glioma stem cells and mircovessels within different growth stages of subcutaneous tumor.
Stem cell medium culture and magnetic activated cell sorting were carried out to obtain CD133+ cells from C6 rat glioma cell line. Sprague Dawley (SD) rat ears model were established to observe glioma stem cells promoting blood vessel formation. Subcutaneous glioma model of C6 and immunohistochemical staining of hypoxia inducible factor-1α (HIF-1α) and CD133 were used to investigate the relationship between distribution of glioma stem cells and mircovessels. Expressions of CD133 protein in each stage of the subcutaneous tumor were detected by Western blot.
Isolation and identification of glioma stem cells deprived from C6 glioma cell line successfully, the establishment of ears model showed real-time dynamic observation of CD133+ cells involved in angiogenesis and tumor formation. SD rat model of subcutaneous glioma showed the initial of tumor formation, CD133+ cells scattered. With tumor growth, CD133+ cells began to tend to capillaries, in late distributed clusters in perivascular. Meanwhile as tumor growth, CD133 protein expression was gradually increased: the values of Western blot analysis of CD133 expression on 6, 9, 12, 15, 20 d were 0.208±0.004, 0.282±0.003, 0.360±0.004, 0.564±0.135, 0.756±0.007, the differences were significant between different groups (F=2601.681, P<0.01). At a high magnification, the CD133 scores with immunohistochemical staining on 6, 9, 12, 15 d were 0.8±0.4, 2.4±0.5, 4.0 ± 0.7, 6.0±0.7; HIF-1α scores were 0.8±0.4, 2.8±0.8, 5.0±0.7, 6.8±0.4. By Spearman rank correlation analysis found that the relationship between CD133 and HIF-1α expression was positively correlated (r=0.921, P<0.01).
Glioma stem cells promote angiogenesis more than non-stem cells; HIF-1α and its downstream gene product might mediate the distribution of glioma stem cells around the perivascular.
Zhonghua wai ke za zhi [Chinese journal of surgery] 05/2012; 50(5):452-6.
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Ana Camelo,
Jillian L Barlow,
Lesley F Drynan,
Daniel R Neill,
Sarah J Ballantyne,
See Heng Wong,
Richard Pannell, Wei Gao,
Keely Wrigley,
Justin Sprenkle,
Andrew N J McKenzie
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ABSTRACT: BACKGROUND: Interleukin-25 (IL-25) is a potent activator of type-2 immune responses. Mucosal inflammation in ulcerative colitis is driven by type-2 cytokines. We have previously shown that a neutralizing anti-IL-25 antibody abrogated airways hyperreactivity in an experimental model of lung allergy. Therefore, we asked whether blocking IL-25 via neutralizing antibodies against the ligand or its receptor IL-17BR could protect against inflammation in an oxazolone-induced mouse model of colitis. METHODS: Neutralizing antibodies to IL-25 or IL-17BR were administered to mice with oxazolone-induced colitis, a model of ulcerative colitis. The disease onset was evaluated by weight loss and degree of colon ulceration. Also, lamina propria and mesenteric lymph node (MLN) infiltrates were assessed for mucosal inflammation and cultured in vitro to determine cytokine production. RESULTS: We found that in oxazolone colitis IL-25 production derives from intestinal epithelial cells and that IL-17BR(+) IL-13-producing natural killer T (NKT) cells and nuocytes drive the intestinal inflammation. Blocking IL-25 signalling considerably improved the clinical aspects of the disease, including weight loss and colon ulceration, and resulted in fewer nuocytes and NKT cells infiltrating the mucosa. The improved pathology correlated with a decrease in IL-13 production by lamina propria cells, a decrease in the production of other type-2 cytokines by MLN cells, and a decrease in blood eosinophilia and IgE. CONCLUSION: IL-25 plays a pro-inflammatory role in the oxazolone colitis model, and neutralizing antibodies to IL-25 or IL-17BR can slow the ongoing inflammation in this disease. Because this model mimics aspects of human ulcerative colitis, these antibodies may represent potential therapeutics for reducing gut inflammation in patients.
Journal of Gastroenterology 04/2012; · 4.16 Impact Factor
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ABSTRACT: To explore the early changes of arterial elasticity in initial hypertension through two different methods.
A total of 76 hypertensive patients (Grade 1-2, n = 32) were assigned into hypertension group while the age and gender-matched healthy population was selected as normal group (n = 44). All of them were monitored for baPWV in right carotid artery by wave intensity technique. The parameters of two methods were compared between two groups.
Higher bi-lateral baPWV were found in the hypertension group (right: (1472 ± 198) m/s vs (1353 ± 233) m/s), (left: (1465 ± 198) m/s vs (1353 ± 241) m/s) (P < 0.05). Compared with the normal group, Patients in the hypertension group had statistically higher W(1) ((9.8 ± 3.8)×10(3) mm Hg×m×s(-3) vs (7.4 ± 2.4)×10(3)) mm Hg×m×s(-3), W(2) ((2.8 ± 1.1)×10(3) mm Hg×m×s(-3) vs (2.0 ± 1.0)×10(3) mm Hg×m×s(-3)), stiffness parameter (β) ((6.9 ± 2.6) vs (5.1 ± 1.3)), pressure-strain elastic modulus (Ep) ((99 ± 39) kPa vs (57 ± 17) kPa), one-point wave velocity (PWVβ) ((6.0 ± 1.1) m/s vs (4.6 ± 0.6) m/s), PWVWI ((6.2 ± 1.4) m/s vs (4.4 ± 1.0) m/s) (P < 0.01). R-W(1) ((100 ± 14) ms vs (103 ± 13) ms), (W(1)-W(2)) ((261 ± 20) ms vs (274 ± 15) ms) and arterial compliance (AC) ((0.8 ± 0.4) mm(2)/kPa vs (1.1 ± 0.3) mm(2)/kPa) in the hypertension group were statistically lower than those of the normal group (P < 0.05).
The initial hypertensive patients may have impaired arterial elasticity during an early stage.
Zhonghua yi xue za zhi 03/2012; 92(11):764-7.
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ABSTRACT: Baseline white blood cell (WBC) count was correlated with ischemic events occurrence in patients with ST-elevated myocardial infarction (STEMI). However, circulating WBC count is altered after percutaneous coronary intervention (PCI). The aim of this study was to assess the relationship between postprocedural WBC count and clinical outcomes in STEMI patients who underwent PCI.
A total of 242 consecutive acute STEMI patients who underwent successful primary PCI were enrolled and followed up for two years. WBC counts were measured within 12 hours after PCI. ST-segment resolution (ST-R) and myocardial blush grades (MBG) were evaluated immediately after PCI. Left ventricular ejection fraction (LVEF) was obtained at baseline and 12 - 18 months after PCI.
Postprocedural WBC count was an independent inverse predictor of ST-R (OR 0.80, P < 0.0001) and MBG 3 (OR 0.82, P < 0.0001). It was negatively correlated with LVEF (baseline r = -0.22, P = 0.001; 12 - 18 months r = -0.29, P < 0.0001). The best cutoff value of WBC for predicting death was determined to be 13.0 × 10(9)/L. The patients with a postprocedural WBC count above 13.0 × 10(9)/L showed a significantly lower cumulative survival rate (30 days, 82.4% vs. 99.0%, P < 0.0001 and 2 years 75.0% vs. 96.4%, P < 0.0001). Multivariate Cox regression analysis showed that a postprocedural WBC count was a strong independent predictor of 30-day mortality (HR 8.48, P = 0.019) and 2-year mortality (HR 4.93, P = 0.009).
Increased postprocedural WBC count is correlated with myocardial malperfusion and left ventricular dysfunction, and is an independent predictor of poor clinical outcomes in STEMI patients who underwent PCI.
Chinese medical journal 03/2012; 125(6):1023-9. · 0.86 Impact Factor
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ABSTRACT: Little is known about the effect of effort-reward imbalance (ERI) on fibrinogen. We aimed to examine the association between ERI and fibrinogen among Chinese workers.
A total of 732 subjects without vascular diseases were analyzed. Associations between job stress evaluated by ERI model and plasma fibrinogen were explored by multiple regression.
Effort, overcommitment, and ERI were significantly positively associated with fibrinogen, while reward was negatively related with fibrinogen both for men and for women. Compared with low level group, high level of effort, overcommitment, and ERI significantly increased risk of elevated fibrinogen (more than mean concentration) with adjusted OR of 3.3, 12.5, and 7.7 for men; 2.9, 7.2, and 7.2 for women, respectively; however, high reward reduced 80% risk for elevated fibrinogen.
Effort, overcommitment, and ERI are significantly associated with fibrinogen among Chinese workers. High fibrinogen may be a possible link between job stress and cardiovascular disease.
American Journal of Industrial Medicine 02/2012; 55(2):167-75. · 1.63 Impact Factor
