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Xiaobin Luo,
Zhenwei Pan,
Hongli Shan,
Jiening Xiao,
Xuelin Sun,
Ning Wang,
Huixian Lin,
Ling Xiao,
Ange Maguy,
Xiao-Yan Qi, [......],
Yong Zhang,
Yunlong Bai,
Jing Ai,
Lihua Sun,
Hang Lu,
Xiao-Yan Luo,
Zhiguo Wang,
Yanjie Lu,
Baofeng Yang,
Stanley Nattel
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ABSTRACT: Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Inward-rectifier K+ current (IK1) is believed to be an important regulator of reentrant-spiral dynamics and a major component of AF-related electrical remodeling. MicroRNA-26 (miR-26) is predicted to target the gene encoding KIR2.1, KCNJ2. We found that miR-26 was downregulated in atrial samples from AF animals and patients and this downregulation was accompanied by upregulation of IK1/KIR2.1 protein. miR-26 overexpression suppressed expression of KCNJ2/KIR2.1. In contrast, miR-26 knockdown, inhibition, or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-26 target. Knockdown of endogenous miR-26 promoted AF in mice, whereas adenovirus-mediated expression of miR-26 reduced AF vulnerability. Kcnj2-specific miR-masks eliminated miR-26-mediated reductions in Kcnj2, abolishing miR-26's protective effects, while coinjection of a Kcnj2-specific miR-mimic prevented miR-26 knockdown-associated AF in mice. Nuclear factor of activated T cells (NFAT), a known actor in AF-associated remodeling, was found to negatively regulate miR-26 transcription. Our results demonstrate that miR-26 controls the expression of KCNJ2 and suggest that this downregulation may promote AF.
The Journal of clinical investigation 04/2013; · 15.39 Impact Factor
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Bo Sun,
Rong Huo,
Yue Sheng, Yue Li,
Xin Xie,
Chang Chen,
Hui-Bin Liu,
Na Li,
Cheng-Bo Li,
Wen-Ting Guo,
Jiu-Xin Zhu,
Bao-Feng Yang,
De-Li Dong
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ABSTRACT: Identifying the key factor mediating pathological cardiac hypertrophy is critically important for developing the strategy to protect against heart failure. Bone morphogenetic protein-4 (BMP4) is a mechanosensitive and proinflammatory gene. In this study, we investigated the role of BMP4 in cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. The in vivo pathological cardiac hypertrophy models were induced by pressure-overload and angiotensin (Ang) II constant infusion in mice, and the in vitro model was induced by Ang II exposure to cultured cardiomyocytes. The expression of BMP4 increased in pressure overload, Ang II constant infusion-induced pathological cardiac hypertrophy, but not in swimming exercise-induced physiological cardiac hypertrophy in mice. BMP4 expression also increased in Ang II-induced cardiomyocyte hypertrophy in vitro. In turn, BMP4 induced cardiomyocyte hypertrophy, apoptosis, and cardiac fibrosis, and these pathological consequences were inhibited by the treatment with BMP4 inhibitors noggin and DMH1. Moreover, Ang II-induced cardiomyocyte hypertrophy was inhibited by BMP4 inhibitors. The underlying mechanism that BMP4-induced cardiomyocyte hypertrophy and apoptosis was through increasing NADPH oxidase 4 expression and reactive oxygen species-dependent pathways. Lentivirus-mediated overexpression of BMP4 recapitulated hypertrophy and apoptosis in cultured cardiomyocytes. BMP4 inhibitor DMH1 inhibited pressure overload-induced cardiac hypertrophy in mice in vivo. The plasma BMP4 level of heart failure patients was increased compared with that of subjects without heart failure. In summary, we conclude that BMP4 is a mediator and novel therapeutic target for pathological cardiac hypertrophy.
Hypertension 12/2012; · 6.21 Impact Factor
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International journal of cardiology 10/2012; · 7.08 Impact Factor
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ABSTRACT: Accumulating evidence suggests that the adrenergic receptors (ARs) play an important role in cardiac diseases. The expression of β3-AR has been recently demonstrated in atria, however, its role in atrial structural remodeling of atrial fibrillation (AF) is unclear. Therefore, the present study was designed to investigate the role of β3-AR in atrial structural remodeling in AF and to clarify its possible mechanisms. Twenty-eight dogs were randomly divided into sham, pacing, β3-AR agonist (BRL37344) and β3-AR antagonist (L748337) groups. AF was induced by rapid atrial pacing at 600 beats per minute for 3 weeks and evaluated by determining the ultrastructure and function of atria. The expression of β3-AR and p38 mitogen-activated protein kinase (MAPK) was examined by western blot, immunohistochemistry and real-time RT-PCR. Additionally, the extent of oxidative stress was tested. We found the atrial enlargement and dysfunction in pacing group. Moreover, atrial interstitial fibrosis, apoptosis and oxidative stress were increased and the levels of β3-AR and phosphorylated p38 MAPK were increased after pacing. Activation of β3-AR exacerbated the pathologic changes and oxidative stress, which were effectively inhibited by L748337. We concluded that β3-AR was upregulated in paced atria, which contributed to oxidative stress and exacerbated atrial structural remodeling by regulating p38 MAPK. Our study provides novel insights into the pharmacological role of β3-AR in AF.
Cellular Physiology and Biochemistry 07/2012; 30(2):372-81. · 2.86 Impact Factor
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Jing Ai,
Rong Zhang,
Xu Gao,
Hui-Fang Niu,
Ning Wang,
Yi Xu, Yue Li,
Ning Ma,
Li-Hua Sun,
Zhen-Wei Pan,
Wei-Min Li,
Bao-Feng Yang
[show abstract]
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ABSTRACT: The purpose of the present study was to evaluate the effects of overexpression of microRNA-1 (miR-1) on cardiac contractile function and the potential molecular mechanisms.
Transgenic (Tg) mice (C57BL/6) for cardiac-specific overexpression of miR-1 driven by the α-myosin heavy chain promoter were generated and identified by real-time reverse-transcription polymerase chain reaction with left ventricular samples. We found an age-dependent decrease in the heart function in Tg mice by pressure-volume loop analysis. Histological analysis and electron microscopy displayed short sarcomeres with the loss of the clear zone and H-zone as well as myofibril fragmentation and deliquescence in Tg mice. Further studies demonstrated miR-1 post-transcriptionally down-regulated the expression of calmodulin (CaM) and cardiac myosin light chain kinase (cMLCK) proteins by targeting the 3'UTRs of MYLK3, CALM1, and CALM2 genes, leading to decreased phosphorylations of myosin light chain 2v (MLC2v) and cardiac myosin binding protein-C (cMyBP-C). Knockdown of miR-1 by locked nucleic acid-modified anti-miR-1 antisense (LNA-antimiR-1) mitigated the adverse changes of cardiac function associated with overexpression of miR-1.
miR-1 induces adverse structural remodelling to impair cardiac contractile function. Targeting cMLCK and CaM likely underlies the detrimental effects of miR-1 on structural components of muscles related to the contractile machinery. Our study provides the first evidence that miRNAs cause adverse structural remodelling of the heart.
Cardiovascular research 06/2012; 95(3):385-93. · 5.80 Impact Factor
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ABSTRACT: During sevoflurane anesthesia with Sofnolime for CO(2) absorption, the factors affecting the production of compound A (a chemical is nepherotoxic) are still not clear. This study is designed to investigate the effects of different fresh gas flow during induction, the vital capacity induction (VCI) vs. the tidal volume breath induction (TBI) on the compound-A production with a fresh Sofnolime or a dehydrated Sofnolime using a simulated lung model.
The experiments were randomly divided into four groups: group one, VCIf, vital capacity fresh gas inflow with fresh Sofnolime; group two, TBIf, tidal volume breath fresh gas inflow with fresh Sofnolime; group three, VCId, vital capacity fresh gas inflow with dehydrated Sofnolime, and group four, TBId, tidal volume breath fresh gas inflow with dehydrated Sofnolime. The inspired sevoflurane was maintained at 8%, the concentrations of compound-A were assayed using Gas-spectrum technique, and Sofnolime temperatures were monitored at 1-min intervals throughout the experiment.
The mean and maximum concentrations of compound A were significantly higher in the vital capacity group than the tidal volume breath group (P<0.01). At the beginning of anesthesia maintenance, the compound-A concentration in group VCIf was 36.28±6.13 ppm, which was significantly higher than the 27.32±4.21 ppm observed in group TBIf (P<0.01). However, these values decreased to approximately 2 ppm in the dehydrated Sofnolime groups. Sofnolime temperatures increased rapidly in the dehydrated Sofnolime groups but slowly in the fresh Sofnolime groups.
With fresh Sofnolime, vital capacity induction increased compound-A production in the circuit system compared with tidal volume breath induction. However, with dehydrated Sofnolime, the effects of the two inhalation induction techniques on compound-A output were not significantly different.
International journal of medical sciences 01/2012; 9(6):435-40. · 2.24 Impact Factor
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ABSTRACT: This study was designed to investigate the effects and mechanism of action of the traditional Chinese drug formula, qiliqiangxin (QLQX), on cardiac function in spontaneously hypertensive rats (SHRs).
We evaluated the effects of oral high-dose (4 g/kg/day, n = 7) and low-dose (1 g/kg/day, n = 7) QLQX on cardiac function in SHRs aged between 8 compared to control, the 8-week-old Wistar-Kyoto (WKY) rats. Echocardiography was performed to evaluate cardiac function and hemodynamic parameters. Hematoxylin and eosin (HE) and Masson's trichrome staining were performed, and the expression of myocardial angiotensin (Ang)-converting enzyme, chymase, transforming growth factor (TGF)-β, and collagen-type I and III were evaluated with real-time reverse transcription-PCR. Myocardial chymase, Ang-converting enzyme (ACE), and Ang II activities were measured with radioimmunoassay (RIA) techniques. Cardiac mast cells were detected with toluidine blue staining.
In SHRs, the number of chymase enzyme-positive mast cells increased in the left ventricle (LV) compared with WKY rats. QLQX significantly decreased mast cell density and cardiac chymase levels, and it improved ejection fraction values and cardiac systolic function compared with vehicle. Moreover, QLQX decreased left atrial diameters and improved the E/A ratio. QLQX suppressed collagen-type I and III and TGF-β mRNA levels, and Ang II activity, in a dose-dependent manner. Whereas no difference in ACE activity was found between SHRs, chymase expression and activity were significantly decreased with QLQX.
These data suggest that QLQX improves both systolic and diastolic cardiac function in SHRs through downregulating the cardiac chymase signaling pathway and chymase-mediated Ang II production.
American Journal of Hypertension 11/2011; 25(2):250-60. · 3.18 Impact Factor
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ABSTRACT: Sevoflurane is currently used as a volatile inhalation anesthetic with many clinical advantages. A representative degradation product, compound A, was quantitatively measured to investigate whether there are different reactions between two kinds of water content sevoflurane formulations with different carbon dioxide (CO2) absorbents.
A closed-circle breathe bag with the Dräger Fabius GS anesthesia apparatus was used as an artificial rubber lung. The experiments were grouped according to different sevoflurane formulations: group A: higher-water sevoflurane (Ultane); group B: lower-water sevoflurane (Sevoness). During the experiment, CO2 (200 ml/min) was continually perfused to keep the end-tidal pressure of CO2 (P(ET)CO2) at 35 - 45 mmHg. The artificial ventilation was set to 6 L/min, and the breathing rate at 12 breaths/min. The circuit was operated with constant fresh gas flow rate (1 L/min) and the sevoflurane concentration was kept at 1.0 minimum alveolar concentration (MAC) for 240 minutes. At 0, 10, 20, 30, 60, 90, 120, 180 and 240 minutes, gas was collected from the Y-piece. Gas chromatography/mass spectrometry (GC/MS) was used to quantify the major degradation product, compound A, with different water content sevoflurane. PETCO2 and sevoflurane concentration, and the temperature of the canister were continuously monitored during the experiment.
There were no significant differences in P(ET)CO2 and sevoflurane concentrations between the two groups. Drägersorb 800 plus produced the highest concentrations of compound A compared with other sodalimes, and Sevoness in Drägersorb 800 plus generated more compound A than Ultane (P < 0.05). There were significant differences in the peak and average compound A concentrations between Ultane and Sevoness with Drägersorb 800 plus (P < 0.05), while the compound A concentration produced by Sodasorb grase and sofonolime in the two groups showed no significant difference (P > 0.05). In the same group, the peak and average of compound A concentration produced by Sodasorb grase and sofonolime showed significant difference with Drägersorb 800 plus (P < 0.05).
The water content of sevoflurane and potassium hydroxide in CO2 absorbent can influence compound A production.
Chinese medical journal 04/2011; 124(7):1050-4. · 0.86 Impact Factor
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ABSTRACT: Cardiac electrophysiological function is under the regulatory control of the sympathetic nervous system. In addition to classical β-adrenoceptors (β-AR, including β(1)- and β(2)- subtypes), β(3)-AR is also expressed in human heart and shows its distinctive functions. This study is aimed to elucidate the role of β(3)-AR in the regulation of atrial fibrillation (AF), especially its role in rapid pacing-induced atrial electrical remodeling in rabbits. The rapid atrial pacing model was established by embedding electrodes in the right atrium pacing at a speed of 600 beats per minute. The protein level of β(3)-AR in the atria was found significantly upregulated by western blot. The atrial effective refractory period (AERP) and its rate adaptation were decreased after pacing which were further shortened by BRL37344, a selective β(3)-AR agonist, leading to the increase of AF inducibility and duration. Similarly, β(3)-AR activation induced time-dependent shortening of action potential duration (APD), together with decrease of L-type calcium current (I(Ca,L)) and increase of inward rectifier potassium current (I(K1)) and transient outward potassium current (I(to)) in rapid pacing atrial myocytes. Meanwhile, all the effects were abolished by specific β(3)-AR antagonist, SR59230A. In summary, our study represents that activation of β(3)-AR promotes the atrial electrical remodeling process by altering the balance of ion channels in atrial myocytes, which provides new insights into the pharmacological role of β(3)-AR in heart diseases.
Cellular Physiology and Biochemistry 01/2011; 28(1):87-96. · 2.86 Impact Factor
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ABSTRACT: To explore the role of homocysteine in the pathogenesis of alcoholic cardiomyopathy.
A total of 69 male Wistar rats were randomly assigned into two groups: alcohol-fed group and the control. Cardiac function was assessed by pulse Doppler. Plasma Hcy levels were examined using automatic biochemical instrument (chemiluminescence). The protein expression of MMP-9 was evaluated using immunohistochemical method, and collagen fiber of myocardium was quantitative analyzed by Masson stain.
After heavy drinking, the LVEDd of alcohol-fed group were larger than the control group [(7.0±0.6) mm vs (5.0±0.4) mm, P<0.05], the LVEF and FS were lower in the 4th month (52%±8% vs 78%±4%, 31%±3% vs 47%±2%, P<0.05), the data changed more significantly (P<0.01) in the 6th month. The level of plasma Hcy from alcohol-fed group was significantly higher from the 2nd month than that before the experiment [(18.1±3.1) µmol/L vs (9.8±2.1) µmol/L, P<0.01], and it was higher in 4th month than that in 2nd month [(26.3±4.0) µmol/L vs (18.1±3.1) µmol/L, P<0.05], it was highest in 6 months. After 4-month and 6-month drinking, the expression of MMP-9 protein from alcohol group was higher than before the experiment (0.161%±0.019%, 0.263%±0.014% vs 0.050%±0.008%, P<0.01). Masson staining showed myocardial collagen of alcohol group was more after 4-month and 6-month drinking than those before the experiment (10.23%±1.20% vs 0.50%±0.09%; 22.41%±2.57% vs 0.50%±0.09%, P<0.01). Plasma Hcy and cardiac tissue MMP-9 is a significant positive correlation (r=0.848, P<0.01).
Long-term and large drink liquor can lead to plasma Hcy levels significantly increased, and participate cardiac remodeling and the pathogenesis of ACM through increasing the expression of myocardial tissue MMP-9 protein.
Zhonghua yi xue za zhi 01/2011; 91(4):272-6.
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ABSTRACT: To evaluate the outcome of ST-elevation acute myocardial infarction (STEMI) patients complicated pre-hospital cardiac arrest underwent percutaneous coronary intervention (PCI).
From September 2004 to November 2008, 1446 consecutive patients with acute STEMI underwent PCI in our department. 49 out of 1446 patients complicated by pre-hospital cardiac arrest. Clinical outcome including total mortality, adverse cardiac events, stroke and bleeding events during the hospitalization period and within 1 year after discharge was compared between patients with or without pre-hospital cardiac arrest.
PCI success rate was similar (85.7% vs. 88.8%, P = 0.497) while the incidence of in-hospital cardiogenic shock 22.4% vs. 3.0%, P < 0.001 and cardiac arrest (44.9% vs. 5.9%, P < 0.001) and in-hospital mortality (36.7% vs. 2.0%, P < 0.001) were significantly higher in patients with pre-hospital cardiac arrest than patients without pre-hospital cardiac arrest. Time from symptom onset to emergency treatment, asystole as initial rhythm, Glasgow coma scale (GCS ≤ 7) and cardiogenic shock on admission were independent risk factors of in-hospital death in patients with pre-hospital cardiac arrest. During follow up, incidences of overall mortality, re-infarction, revascularization and stroke were similar between the two groups.
STEMI patients with pre-hospital cardiac arrest undergoing emergency PCI are facing higher risk of cardiogenic shock and cardiac arrest and higher in-hospital mortality compared to those without pre-hospital cardiac arrest. However, the post-hospital discharge outcome was similar between the two groups.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 10/2010; 38(10):875-9.
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ABSTRACT: Vital capacity induction and tidal breathing induction are currently administered for inhalation induction of anesthesia with sevoflurane. The aim of this study was to compare them using sevoflurane with respect to induction time, complications of inhalation induction, and compound A production in adult patients.
Fifty-one women with American Society of Anesthesiologists physical status I-II undergoing mammary gland tumorectomy were randomly assigned to receive either vital capacity induction or tidal breathing induction with 8% sevoflurane at 6 L/min followed by laryngeal mask airway insertion. Induction times, complications of inhalation induction, and vital signs were recorded. Inspired concentrations of compound A were assayed and sofnolime temperatures were monitored at one-minute intervals after sevoflurane administration.
The time to loss of eyelash reflex was significantly shorter with the vital capacity induction technique than with the tidal breathing induction technique ((43.8 ± 13.4) seconds vs. (70.8 ± 16.4) seconds, respectively; P < 0.01). Cardiovascular stability was similar in both groups. The incidence of complications was significantly less with the vital capacity induction technique than with the tidal breathing induction technique (7.7% vs. 32%, respectively; P < 0.01). However, the mean and maximum concentrations of compound A during induction were significantly higher in the vital capacity group than those in the tidal breathing group (P < 0.05); compound A concentration at the beginning of anesthesia maintenance was (40.73 ± 10.83) ppm in the vital capacity group and (29.45 ± 7.51) ppm in tidal breathing group (P = 0.019).
For inhalation induction of anesthesia, the vital capacity induction was faster and produced fewer complications than that for tidal breathing induction, but increased compound A production in the circuit system.
Chinese medical journal 09/2010; 123(17):2336-40. · 0.86 Impact Factor
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ABSTRACT: To investigate the association between beta(3)-adrenergic receptor (beta(3)-AR) and oxidative stress in isoproterenol (ISO)-induced chronic heart failure (HF) rats.
Seven weight-matched normal adult rats (control), 18 ISO induced heart failure rats and 21 ISO induced heart failure rats treated with specific beta(3)-AR inhibitor, SR59230A for 6 weeks were included in this study. Echocardiography was performed at the end of the study and the myocardial levels of total superoxide dismutase (T-SOD) and lipid peroxidation (LPO) were measured by colorimetry, myocardial expression of beta(3)-AR was detected by reverse transcription-polymerase chain reaction (RT-PCR).
Compared with control group, the cardiac function was significantly reduced and myocardial beta(3)-AR mRNA expression was significantly increased, LPO level was also significantly enhanced while T-SOD level was significantly reduced in ISO group and these changes could be significantly attenuated by treatment with SR59230A.
Our results showed that myocardial upregulation of beta(3)-AR is associated with increased oxidative stress in this model and beta(3)-AR inhibitor may be a new therapeutic agent for heart failure treatment.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 05/2010; 38(5):435-9.
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Jianqiang Li, Yue Li,
Jie Liu,
Hongbo Shan,
Weimin Li,
Jiyi Zhao,
Yongtai Gong,
Li Sheng,
Deli Dong,
Baoxin Li,
Baofeng Yang
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ABSTRACT: Previous studies have demonstrated that elevated thyroid hormones lead to atrial electrical remodelling, which makes the atria prone to fibrillation. The present study was undertaken to clarify whether atrial structural and sympathetic remodelling, which also contribute to the development of atrial fibrillation, occur during hyperthyroidism. Fourteen dogs were divided into a hyperthyroid group and a euthyroid group. Dogs in the hyperthyroid group were given levothyroxine sodium tablets for 10 weeks, while those in the euthyroid group received starch placebos. Parameters defining thyroid status were recorded weekly. Electrophysiological properties, tissue structure and ultrastructure, sympathetic innervation, levels of apoptosis-related proteins and calpain-1 were assessed in the atria. After the 10-week period of thyroid feeding, atrial dilatation and dysfunction were observed in the hyperthyroid group. Compared with atrial myocytes obtained from the euthyroid group, those from the hyperthyroid group had fewer sarcomeres and showed a significant increase in myolysis, fibrosis, and apoptosis. The levels of caspase-3, bax, calpain-1, and tyrosine hydroxylase (a marker of sympathetic nerves) were increased in the hyperthyroid group, while that of bcl-2 was decreased. We conclude that elevated thyroid hormones contribute to atrial structural and sympathetic remodelling, which have the potential to promote the development of atrial fibrillation.
Acta histochemica 01/2010; · 1.23 Impact Factor
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ABSTRACT: No-reflow phenomenon during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is a predictive factor of continuous myocardial ischemia, ventricular remodeling and cardiac dysfunction, which is closely associated with a worse prognosis. This study aimed to evaluate intracoronary nitroprusside in the prevention of the no-reflow phenomenon in AMI.
Ninety-two consecutive patients with AMI, who underwent primary PCI within 12 hours of onset, were randomly assigned to 2 groups: intracoronary administration of nitroprusside (group A, n = 46), intracoronary administration of nitroglycerin (group B, n = 46). The angiographic results were observed. The real-time myocardial contrast echocardiography (RT-MCE), including contrast score index (CSI), wall motion score index (WMSI), transmural contrast defect length (CDL) and serious WM abnormal length (WML) were recorded at 24 hours and 1 week post-PCI. High sensitivity C-reactive protein (Hs-CRP) was examined by immune rate nephelometry. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was tested with enzyme-linked immunosorbent assay. Patients were followed up for six months. Major adverse cardiac events (MACE) were recorded.
The incidence of final TIMI-3 flow in group A was much higher than that in Group B (P < 0.05), final corrected TIMI frame count (cTFC) in group A decreased significantly than that in group B (P < 0.01). The CSI, CDL/LV length, WMSI and WL/LV length in group A were significantly lower than that in group B (P < 0.01). Levels of Hs-CRP and NT-proBNP at 1 week post-PCI decreased significantly in group A than that in group B (P < 0.01). Patients were followed up for 6 months and the incidence of MACE in group A was significantly lower than that in group B (P < 0.05).
Intracoronary nitroprusside can improve myocardial microcirculation, leading to the decrease of the incidence of no-reflow phenomenon and better prognosis.
Chinese medical journal 11/2009; 122(22):2718-23. · 0.86 Impact Factor
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Jing Ai,
Rong Zhang, Yue Li,
Jielin Pu,
Yanjie Lu,
Jundong Jiao,
Kang Li,
Bo Yu,
Zhuqin Li,
Rongrong Wang,
Lihong Wang,
Qiang Li,
Ning Wang,
Hongli Shan,
Zhongyu Li,
Baofeng Yang
[show abstract]
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ABSTRACT: Recent studies have revealed the role of microRNAs (miRNAs) in a variety of basic biological and pathological processes and the association of miRNA signatures with human diseases. Circulating miRNAs have been proposed as sensitive and informative biomarkers for multiple cancers diagnosis. We have previously documented aberrant up-regulation of miR-1 expression in ischemic myocardium and the consequent slowing of cardiac conduction. However, whether miR-1 could be a biomarker for predicting acute myocardial infarction (AMI) is unclear. In the present study, we recruited 159 patients with or without AMI for quantification of miR-1 level in plasma using real-time RT-PCR method. We performed Wilcoxon rank sum and signed rank tests for comparison. Univariable linear regression and logistics regression analyses were performed to assess the potential correlation between miR-1 and known AMI markers. We also conducted receiver–operator characteristic curve (ROC) analysis to evaluate the diagnostic ability of miR-1. We found that: miR-1 level was significantly higher in plasma from AMI patients compared with non-AMI subjects and the level was dropped to normal on discharge following medication. Increased circulating miR-1 was not associated with age, gender, blood pressure, diabetes mellitus or the established biomarkers for AMI. However, miR-1 level was well correlated with QRS by both univariable linear and logistics regression analyses. The area under ROC curve (AUC) was 0.7740 for separation between non-AMI and AMI patients and 0.8522 for separation AMI patients under hospitalization and discharge. Collectively, our results revealed that circulating miR-1 may be a novel, independent biomarker for diagnosis of AMI.
Biochemical and Biophysical Research Communications 11/2009; · 2.48 Impact Factor
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ABSTRACT: This study was designed to evaluate the effects of a calpain inhibitor on cardiac muscle apoptosis in rapid pacing canine atrial fibrillation (AF) models.
Twenty one dogs were divided into three groups: a sham operation group, a control AF group and a calpain inhibitor group. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute. N-Acetyl-Leu-Leu-Met (1.0 mg/kg/day) was administered in the calpain inhibitor group for three weeks. The activity of calpain I and cardiomyocyte apoptosis were measured by fluorometry and TUNEL assay, respectively. Protein expression of caspase-3 was detected by Western blot. The localizations of caspase-3, caspase-8, bcl-2 and ARC were assessed by immunohistochemistry.
In comparison to the sham operation group, the activity of calpain I was significantly increased in the control AF group (2.3 fold, p < 0.001), and decreased in the calpain inhibitor group (1.1 fold, p < 0.005). The calpain activity correlated with the apoptosis index (r = 0.9, p < 0.05). The apoptosis index was 1.0 +/- 0.2%, 11.8 +/- 6.8% and 3.5 +/- 2.1% in the sham operation group, control AF group and calpain inhibitor group, respectively. In the sham operation group, control AF group and calpain inhibitor group, the expressions of caspase-3 (13.0 +/- 1.9%, 52.8 +/- 4.3% and 33.6 +/- 3.7%), caspase-8 (40.1 +/- 5.3%, 92.6 +/- 6.5% and 55.3 +/- 5.9%), bcl-2 (65.8 +/- 6.1%, 52.0 +/- 5.7% and 69.9 +/- 5.3%) and ARC (70.2 +/- 8.6%, 68.8 +/- 7.3% and 81.5 +/- 8.8%) were calculated as immunohistochemical indexes, respectively.
The calpain inhibitor N-Acetyl-Leu-Leu-Met attenuated apoptosis through a complicated network of apoptosis-related proteins, which may result in improvement of structural remodeling in atrial fibrillation.
Cardiovascular Drugs and Therapy 10/2009; 23(5):361-8. · 3.13 Impact Factor
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ABSTRACT: With the existing fault injection techniques, many faults that can fully expose testability design defects can not be injected. To solve this problem, a method of fault equivalent analysis is proposed. By this means, some characteristics are extracted from the faults those unable to be injected, and ldquoyield analysisrdquo or ldquoyielded analysisrdquo is performed. Then the minimal cut sets of atom faults is obtained and selected, which are finally equivalent to the atom faults sequence. Applications show that the method not only solves the problem that many faults are not able to be injected, but also ensures the effect of testability experiment validation.
Reliability, Maintainability and Safety, 2009. ICRMS 2009. 8th International Conference on; 08/2009
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ABSTRACT: This study was designed to investigate whether IL-17 can regulate the expression of the MMP/TIMP system, the OPG/RANK/RANKL system, or type-I and type-III collagen fibers in a rat model of isoproterenol-induced heart failure (HF). We also investigated the effect of IL-17 on myocardial fibrosis in this model.
HF was induced in Wistar-Kyoto rats by hypodermic injection of isoproterenol (ISO) twice every 24 h. After 2 months, the surviving rats were divided into three groups: monoclonal Anti-IL-17 Ab (100 microg/day), IgG (100 microg/day) or PBS were injected five times every 48 h (i.p.). One day after the last injection, all of the rats were sacrificed. H&E and Masson staining were used to evaluate myocardial fibrosis, and immunohistochemistry was used to measure the levels of MMP-1, TIMP-1, TIMP-4, OPG, RANKL, type-I and type-III collagen fibers. We also treated adult rat cardiac fibroblasts with IL-17 (10 ng/ml), IL-17 (10 ng/ml)+OPG (10 ng/ml), IL-17 (10 ng/ml)+anti-RANKL Ab (100 ng/ml), or PBS for 24 h, realtime RT-PCR was used to measure the expressions of MMP-1.
The expressions of MMP-1, RANKL, and type-I and -III collagen fibers decreased, and the expressions of TIMP-1, TIMP-4, and OPG increased in the Anti-IL-17 group compared to controls. H&E and Masson staining revealed that blockade of IL-17 can improve myocardial fibrosis in HF. IL-17 increased the expression of MMP-1 in cardiac fibroblasts, and OPG and anti-IL-17 Ab could inhibit this function partly. Thus, IL-17 was dependent on the RANKL/OPG system to induce MMP-1 partly.
Our study demonstrates the contribution of IL-17 to myocardial fibrosis in isoproterenol-induced HF. IL-17 can regulate the RANKL/OPG and MMP/TIMP systems in this model. The RANKL/OPG system is one of intermediaries between IL-17 and MMP-1 in cardiac fibroblasts. As a harmful cytokine, anti-IL-17 treatment is a potential therapeutic strategy in HF.
Experimental and Molecular Pathology 07/2009; 87(3):212-8. · 2.42 Impact Factor
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ABSTRACT: Oxidative stress has recently been implicated in atrial fibrillation (AF); however, the mechanisms remain unclear. Herein, we hypothesize that probucol can attenuate atrial structure remodeling.
Twenty dogs were randomly divided into sham-operated, control, and probucol-treated groups. We identified apoptosis and histopathological changes in the atria. Oxidative stress was measured by lipid peroxidation and echocardiographic examinations were performed.
Atrial apoptosis indexes were dramatically decreased in the probucol-treated group compared to the control group. Relative to the control group, the percentage of myolysis was dramatically decreased in the probucol-treated group (p < 0.01). There was less lipid peroxidation in the probucol-treated group than the control group. Atrial function was dramatically elevated in the probucol-treated group.
The results of this study indicate that the antioxidant probucol suppresses atrial structural remodeling and may act as a new therapy for AF.
Biochemical and Biophysical Research Communications 04/2009; 381(2):198-203. · 2.48 Impact Factor
