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ABSTRACT: TZDs (thiazolidinediones) are prescribed as anti-Type II diabetes drugs, but little is known regarding whether TZDs regulate the expression of sPLA2 (secretory phospholipase A2) in macrophages. We have investigated the effects of pioglitazone on LPS (lipopolysaccharide)-induced production of TNF-alpha (tumour necrosis factor alpha), sPLA2-V and -X (groups V and X sPLA2) in RAW 264.7 macrophages. TNF-alpha, sPLA2-V and -X mRNA and protein expression were determined by RT-PCR (reverse transcriptase-PCR) and Western blot analysis, respectively. The activity of NF-kappaB (nuclear factor kappaB) was determined by Western blot and confocal microscopy. LPS induced TNF-alpha, sPLA2-V and sPLA2-X mRNA and protein expression. Pretreatment with 10 mumol/l pioglitazone significantly suppressed LPS-induced TNF-alpha, sPLA2-V and sPLA2-X mRNA and protein expression. LPS induced NF-kappaB expression and translocation in the nucleus, but the inductive effects were inhibited by pioglitazone. Our findings indicate that pioglitazone inhibits production of inflammatory factors induced by LPS in murine macrophage cells by inactivating NF-kappaB. Pioglitazone appears to play an anti-inflammatory role in the atherosclerotic process.
Cell Biology International 09/2009; 34(7):723-30. · 1.48 Impact Factor
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ABSTRACT: To study the effects of chemokine-like factor 1(CKLF1)-plasmid transfer on cardiac function in a rat acute myocardial infarction (AMI) model.
Thirty male SD rats were randomly devided into 3 groups. One hundred micrograms of CKLF1-plasmid, empty plasmid or saline were injected intramuscularly with in vivo electroporation, respectively. Rats were subjected to left coronary artery ligation on the 6th day after gene transfer. Ultrasonic cardiography and hemodynamics were conducted and evaluated on the 22nd day after gene transfer. Then, the animals were sacrificed for determination of percentage of myocardial infarcion.
The left ventricular ejection fraction in CKLF1 group (67.02% +/- 12.24%) was significantly higher than that in the saline group (43.64% +/- 7.82%) and empty plasmid group (47.56% +/- 4.10%), P<0.05. Fractional shortening of left ventricle in CKLF1 group (33.83% +/- 10.15%) was higher than that in saline group (18.49% +/- 3.96%) and empty plasmid group (20.85% +/- 2.24%), P<0.05. The maximal velocity of left ventricular pressure ascensus was higher in CKLF1 group [(5 720.01 +/- 826.32) mmHg/s, 1 mmHg=0.133 kPa] than in saline group [(3 955.69 +/- 685.91) mmHg/s] and in empty plasmid group [(4 412.03 +/- 500.74) mmHg/s)], P<0.05. And the maximal velosity of left ventricular pressure descensus was higher in CKLF1 group [(4 636.23 +/- 407.17) mmHg/s] than in saline group [(2 984.82 +/- 615.24) mmHg/s] and in empty plasmid group [(2 963.87 +/- 419.36) mmHg/s], P<0.05. While the percentage of myocardial infarction in CKLF1 group (29.63% +/- 3.93%) was smaller than that in saline group (38.01% +/- 5.48%) and in empty plasmid group (37.50% +/- 6.33%), P<0.05.
CKLF1 gene transfer can limit the mass of myocardial infarction and improve post-infarction cardiac function.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 04/2009; 41(2):144-7.
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ABSTRACT: To examine the plasma levels of secretory type IIA phospholipase A2 (sPLA(2)-IIA), lipoprotein (a) [Lp(a)], soluble intercellular adhesion molecule-1 (sICAM-1) and soluble platelet endothelial CAM-1 (sPECAM-1), as well as ICAM-1 (K469E) and PECAM-1 (Leu125Val) gene polymorphisms, in patients with unstable angina pectoris (UAP) and stable AP (SAP).
We enrolled 75 patients with SAP, 72 with UAP and 80 controls without angina. Blood samples were obtained before angiography.
The concentrations of sPLA(2)-IIA, sICAM-1 and sPECAM-1 were higher for UAP patients than for SAP patients and controls, and the level of Lp(a) was higher for UAP patients than for controls. Lp(a) and sPLA(2)-IIA levels were significantly correlated, and high plasma Lp(a) level (> or =300 mg/L) was an independent risk factor for angina.
Lp(a) may play an important role in the development of angina. Further research should investigate the role of sPLA(2)-IIA, sICAM-1 and sPECAM-1 in UAP.
Clinical biochemistry 09/2008; 41(18):1423-8. · 2.02 Impact Factor
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ABSTRACT: To explore the relationship between the severity of cardiovascular disease with the expression of apolipoprotein(a) [apo(a)] and apolipoprotein B (apoB) in peripheral blood and their location in peripheral blood cells.
In this report, we selected 4 patients with angiography which indicated that three coronary arteries were narrowed and 5 control patients with normal angiography. Arterial blood was collected and analyzed for lipid parameters in plasma. The mRNA expression of apo(a) and apoB in peripheral white blood cells and platelets were determined by RT-PCR and their protein expression by western blot. Moreover, the expression and location of apo(a) and apoB in white blood cells were determined by confocal microscopy and computer 3D analysis.
In plasma, levels of high density lipo-protein-cholesterol (HDL-C) and polipoprotein A-I(apoA-I) in cardiovascular disease (CVD) patients were significantly less than those in the control patients[(0.62+/-0.05) mmol/L, (0.78+/-0.08) mmol/L vs (0.81+/-0.15) mmol/L, (0.9+/-0.07) mmol/L, P<0.05], but the concentration of other plasma lipid parameters was not different. The size of apo(a) isoforms was not reversely related to the severity of cardiovascular disease and the most commonly occurring phenotype of apo(a) was S4.The expression of apoB in platelets in cardiovascular disease patients was less than that in the control patients by 25.1% (optical density value 0.67+/-0.18 vs 1.00+/-0.10, P<0.05),but the expression of apo(a) was not different between the two groups (optical density value 0.43+/-0.18 vs 0.61+/-0.40, P>0.05). Studies with confocal microscopy indicated that proteins of apo(a) and apoB were co-expressed by a few cells of leukocytes and the ratio of apoB/apo(a) in cardiovascular disease patients was significantly less than that in the control patients (optical density value 1.60+/-0.12 vs 4.40+/-0.35, P<0.05). In platelets and leukocytes, mRNA of apo(a) or apoB was not detectable.
Our studies indicate that peripheral blood cells can carry apo(a) and apoB, furthermore the contents of apoB and apo(a) in cells are different between cardiovascular disease patients and patients with normal coronary artery.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 06/2008; 40(3):245-50.
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ABSTRACT: To investigate the association between the apolipoprotein A5(APOA5) -1131T/C polymorphism and premature coronary heart disease in northern Chinese Han population.
Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE), we analyzed the genotype and allele distribution in 140 patients with premature coronary heart disease diagnosed by coronary angiography and 156 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods.
The allele frequency of APOA5-1131T/C polymorphism in the premature coronary heart disease group was significantly higher (43.2% vs. 33.0%, P=0.011) than that in the control group. Compared with TT homozygotes, CC homozygotes exhibited a 2.809-fold (95% CI 1.331-5.927) increased risk of developing premature coronary heart disease. Logistic regression analysis found that this correlation was independent of sex, age, body mass index (BMI), smoking history as well as serum total cholesterol(TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels; In premature coronary heart disease group, the triglyceride(TG) level in CC homozygotes was significantly higher than those in TC heterozygotes or TT homozygotes.
The APOA5-1131T/C polymorphism has influence on serum TG level, and the APOA5-1131C allele is associated with the development of premature coronary heart disease in northern Chinese Han population.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 01/2008; 39(6):576-80.
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ABSTRACT: To assess the influence of different doses of CKLF1 plasmid on the dynamics and magnitude of the mobilization of the mobilization bone of marrow stem cells in a rat AMI model.
Different doses of plasmid DNA encoding CKLF1 gene, empty plasmid or saline were injected into male SD rats intramuscularly with in vivo electroporation. Rats were subjected to left coronary artery ligation 6 days after gene transfer. Peripheral blood samples were drawn and CD34+ cells were assayed by FACS calibur flow-cytometer. The changes in absolute number of CD34+ cells were evaluated.
Expressions of CKLF1 mRNA and protein were detected in the injection site 7 days after gene transfer. Five days after gene transfer, the CD34+ cells numbers in CKLF1 groups were significantly higher than those in empty plasmid group, especially in CKLF1 100 microg group (16.63x10(6)/L vs 4.98x10(6)/L, P<0.01). On the 5-7 days, the CD34+ cell numbers in CKLF1 groups reached the peak and the peak number was 3.88 times that of baseline in CKLF1 100 microg group (P<0.01). After AMI, the cell numbers of 1 day to 7 days were significantly higher than those of the baseline in empty plasmid group and saline group. In comparison to empty plasmid group, CKLF1 groups were associated with still higher numbers of cells 1 day after AMI (P< 0.05), especially in CKLF1 100 microg group (14.61x10(6)/L vs 7.85x10(6)/L, P<0.01).
CKLF1 gene transfer significantly increases the mobilization of CD34+ stem cells in acute myocardial infarction rats.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 01/2007; 38(6):592-6.
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ABSTRACT: To investigate the effect of hypoxia/reoxygenation on endoplasmic reticulum stress in cultured neonatal rat cardiomyocytes.
Neonatal rat cardiac myocytes in primary culture were exposed to hypoxia for 5.5 hours and subsequently reoxygenation for 2-24 hours. Western blot and RT-PCR were applied to monitor the expression change of GRP78 (glucose regulated protein 78). 2-deoxy-D-glucose (2-DG) was the positive control of this study. Then Western blot and RT-PCR were used to examine the expression of GRP78.
Cell viability was decreased obviously after hypoxia/reoxygenation. Compared with untreated cells, the GRP78 content of the cells had increased significantly in the hypoxia/reoxygenation cells. The level of GRP78 protein and mRNA elevated from the points of 2 hours to 24 hours after reoxygenation, and increased most obviously at the point of 4 hours after reoxygenation. (4 hours: protein level 142% of the control, mRNA level 200%). 2-DG could induce the increasing expression of GRP78 in a concentration-dependent manner from 10-50 mmol/L.
Hypoxia/reperfusion can induce endoplasmic reticulum stress in rat cardiomyocytes.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 09/2005; 37(4):386-8.
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ABSTRACT: Inflammation is a major cause of restenosis after coronary stenting. Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that plays a key role in the tight adhesion between leukocytes and vascular endothelium. The object of this study was to investigate the association between the K469E polymorphism of the ICAM-1 gene and restenosis after coronary stenting in North Chinese population.
The ICAM-1 K469E polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism method in 124 patients who had undergone coronary stenting and coronary angiography at least 3 months earlier. Information on clinical risk factors and procedure-related data were also collected.
Of 124 enrolled patients in total, there were 72 cases of in-stent restenosis. The restenosis rate in this population was 58.1%. The frequencies of the three possible genotypes of the ICAM-1 K469E polymorphism were: KK genotype 50.8%, EE genotype 41.9%, and EK genotype 41.9%. Among restenosis patients, the frequency of the KK genotype was 58.3% and the frequency of E allele carriers was 41.7%. Among non-restenosis patients, the frequency of the KK genotype was 40.4%, and the frequency of E allele carriers was 59.6%. The distribution of these two genotype groups between restenosis and non-restenosis patients was significantly different (P = 0.049). Using multivariate logistic regression, the difference between the two groups was more apparent. The odds ratio of KK homozygotes vs E allele carriers was 2.6, with 95% confidence interval 1.2 - 5.8 (P = 0.018). After grading of risk factors, we found that the KK genotype was a stronger predictor of in-stent restenosis in obesity or hyperlipemia patients, with an odds ratio of 9.3 and 3.7, respectively (P < 0.05).
In our study population, KK homozygotes of the ICAM-1 codon 469 mutation had a higher risk of restenosis after coronary stenting, especially in the case of obese or hyperlipemia patients.
Chinese medical journal 03/2004; 117(2):172-5. · 0.86 Impact Factor
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ABSTRACT: In isolated circular smooth muscles of the guinea-pig stomach, cisapride depolarized the membrane, increased the amplitude and interval of slow waves, and enhanced the cholinergic excitatory junction potential, with no change in the nonadrenergic noncholinergic inhibitory junction potentials. Methysergide mimicked the excitatory actions of cisapride on junction potentials. Results showed that cisapride has dual actions on gastric muscles; excitation by facilitating the release of ACh possibly via 5-HT receptor blockade and also by depolarizing the smooth muscle membrane, and inhibition by reducing the frequency of slow waves, possibly by acting directly on the pacemakers.
Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology.
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ABSTRACT: The effects of trimebutine on the electrical properties of smooth muscle membranes were studied in the isolated rat stomach, the objective being to elucidate the dual actions of this drug on gastric motility. Transmural nerve stimulation elicited a cholinergic excitatory junction potential (e.j.p.) and a nonadrenergic noncholinergic inhibitory junction potential (i.j.p.), and trimebutine inhibited the e.j.p. more than the i.j.p., with no significant change in the acetylcholine-induced depolarization. Trimebutine reduced the interval and, at high concentrations, the amplitude of slow waves. In enzymatically dispersed single cells, the Ca2+ current elicited by depolarization of the membrane was also inhibited by trimebutine. Thus, trimebutine increases slow wave frequency and inhibits cholinergic transmission and Ca2+ influx. The former would enhance while the latter two would depress gastric motility.
European Journal of Pharmacology.
