Apolipoprotein A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases / 中南大学学报(医学版)

Apolipoprotein A5 (Apo A5) is a novel member in apolipoprotein family, which is proven to be an important regulator in triglyceride metabolism, especially in adjusting the TG content in plasma. Apo A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases. The research focuses on -1131T>C, c.56C>G, and c.553G>T.

Efficacy comparison between 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension.</p><p><b>METHODS</b>The study was designed as multicenter, randomized, double-blind, active controlled trial with two parallel groups enrolling 524 participants with mild to moderate essential hypertension. After 2-week run-in period, 186 patients were enrolled and randomly treated with 5 mg perindopril arginine salt and 183 patients were enrolled and randomly treated with 4 mg perindopril tert-butylamine salt. The random sequence was generated by the I.R.I.S., and a balance was made in each center. After double-blind treatment for 8 weeks, the dose could be doubled for patients with uncontrolled BP ((SBP) ≥ 140 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure (DBP) ≥ 90 mmHg) and patients were treated for another 4 weeks.</p><p><b>RESULTS</b>The sitting SBP was similarly decreased by (19.9 ± 17.2) mmHg in perindopril arginine group and (18.5 ± 14.7) mmHg (P = 0.000 5) in perindopril tert-butylamine group post 8 weeks treatment. Dose was doubled in 109 patients (59.9%) in perindopril arginine group and 116 patients (63.7%) in perindopril tert-butylamine group. At 12 weeks post therapy, the sitting SBP decreased by (19.8 ± 16.2) and (19.6 ± 16.3) mmHg respectively in the 2 groups. The decrease of sitting DBP was also similar in both groups (-12.0 ± 10.0) mmHg and (-11.0 ± 8.9) mmHg (P < 0.000 1), respectively. The control rate or response rate was also similar between the two groups (control rate over 8 weeks was 38.5% vs. 31.3%, 95% CI (-2.6-16.9), control rate over 12 weeks was 36.3% vs. 35.7%, 95% CI (-9.3-10.4), response rate over 8 weeks was 64.3% vs. 63.2%, 95% CI (-8.8-11.0), response rate over 12 weeks was 65.9% vs. 64.8%, 95% CI (-8.7-10.9)). Incidence of adverse events was low and similar in both therapy groups.</p><p><b>CONCLUSIONS</b>The results show that perindopril arginine salt 5 mg is as efficient as perindopril tert-butylamine 4 mg on lowering BP for patients with mild to moderate essential hypertension. Both drugs have good safety profile and are well tolerated by patients in this cohort.</p>

Ac-hE-18A-NH2 inhibits the inflammatory response induced by ox-LDL via inhibiting NF-κB activation in RAW264.7 macrophages / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of Ac-hE-18A-NH2 on TNF-α secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms.@*METHODS@#Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 μg/mL) with ox-LDL (50 μg/mL) stimulated. The TNF-α level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and IκB protein -expression in the macrophages were determined by Western blot. NF-κB activity was evaluated by electrophoretic mobility shift assay (EMSA).@*RESULTS@#Ox-LDL stimulation induced a significant increase in TNF-α secretion, mRNA expression, cholesterol accumulation and nuclear factor-κB (NF-κB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-α secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- κB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages.@*CONCLUSION@#Ac-hE-18A-NH2 may suppress TNF-α secretion and mRNA expression in ox-LDL stimulated RAW264.7 macrophages via IκB-NF-κB signaling pathway. The anti-inflammatory effect of Ac-hE-18A-NH2 is better than that of apoA-I mimic peptide D-4F.

Efficacy and safety of fluvastatin extended-release tablets in Chinese patients with hyperlipidemia: a multi-center, randomized, double-blind, double dummy, active-controlled, parallel-group study / 中华内科杂志

Objective To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.Methods In this multi-center,randomized,double-blind,double-dummy,active-controlled,parallel-group study,after 6-week open-label treatment with fluvastatin IR 40 mg once daily,patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.Results (1) There were 218 patients enrolled in each group.At the study endpoint,no statistical difference was found in the mean percent change from baseline for LDL-C with-8.69％ [from (3.504 ±0.060) mmol/L to (3.153 ±0.065) mmol/L] in the fluvastatin XL group and-7.89％ [from (3.491 ±0.050) mmol/L to (3.181 ±0.060) mmol/L] in the fluvastatin IR group (P ＞ 0.05).The 95％ CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70％-3.09％),which was within the pre-specified non-inferiority margin.In the fluvastatin XL group,the proportion of patients with moderate cardiovascular(CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0％ and 31.5％ respectively,while the proportion was 42.5％ and 24.5％ respectively in the fluvastatin IR group.No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters.(2)Similar safety profiles were observed in the two treatment groups,with 21.1％ adverse event (AE) (8.3％ study-drug related AE) in the fluvastatin XL group and 17.0％ AE (6.3％ study-drug related AE) in the fluvastatin IR group.Conclusion The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.

Atorvastatin attenuates involvement of RhoA/Rho-kinase pathway and NF-κB activation in hypoxic pulmonary hypertensive rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypoxic pulmonary hypertension (HPH) contributes to the pathogenesis of cardiopulmonary diseases. Several lines of evidence indicate that the Rho A/Rho-kinase pathway play an important role in the progress of pulmonary hypertension. Stains have been shown exert numerous biological effects that are independent of their cholesterol-lowering property. We hypothesized that the Rho A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH rat model.</p><p><b>METHODS</b>Thirty-two Wistar rats were randomly divided into four groups: control group, hypoxic group, atovastatin group, and normal saline group. The control group was kept in a normoxia environment. The other groups were exposed to hypoxia for three weeks. Atovastatin was administered daily via a gastric gavage in the atovastatin group. We measured the mean pulmonary arterial pressure (mPAP), the ratio of the right ventricular weight to the sum of the weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall thickness/vascular external diameter (WT%), vascular area/total vascular area (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-κB activation in pulmonary vascular smooth muscle cells.</p><p><b>RESULTS</b>Compared with the control group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P < 0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF-κB activation were all positive.</p><p><b>CONCLUSIONS</b>The Rho A/Rho-kinase pathway plays an important role in the development of HPH. Atorvastatin reversed HPH by inhibiting the activity of Rho A/Rho-kinase and NF-κB.</p>

Reduced expression and secretion of apolipoprotein M in fat-fed, streptozotocin-diabetic rats is partially reversed by an artificial ligand of PPARγ / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of administration of rosiglitazone, an artificial ligand of PPARγ, on the expression and secretion of apolipoprotein (apoM) in fat-fed, streptozotocin-treated rats, an animal model for type 2-like diabetes.@*METHODS@#Healthy male SD rats were divided into 4 groups: a control group (n=7), a high-fat chow group (HF group, n=8), a diabetes mellitus group (DM group, n=7), and a diabetes mellitus group with rosiglitazone intervention group (RSG group, n=7). Fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG) and total cholesterol (TC) were measured at the beginning of the study. The diabetic rats model was established by feeding high fat chow and intraperitoneal injection of streprozotocin. Then the randomly selected treatment group was given rosiglitazone by daily gavage for 8 weeks. All the rats were killed at the fifteenth week, at which time blood and tissues (liver, kidney, adipose) were collected and prepared. The levels of FBG, FINS, TG and TC were assayed. The level of apoM in serum was measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to determine apoM mRNA expression in liver, kidney, and adipose tissues.@*RESULTS@#Compared with either control group or HF group, serum apoM concentration in the DM group was reduced significantly (P<0.05); compared with the DM group, however, serum apoM concentrations in RSG group were increased (P<0.05). The expression of apoM mRNA in liver was highest, in kidney medium, and in adipose tissue extremely low (P<0.05). ApoM mRNA expression in liver and kidney was decreased in both DM and HF groups compared to control group (P<0.05). But, as with serum apoM concentration, apoM mRNA in the liver, kidney and adipose tissues of the RSG group were all increased markedly (P<0.05). The level of serum apoM in SD rats correlated negatively with TG (r=-0.466, P=0.011), TC (r=-0.568, P= 0.001), FBS (r =-0.371, P<0.001), and FINS(r=-0.768, P= 0.048 ).@*CONCLUSION@#These results suggest that apoM may participate in the glucose and lipid metabolism by the regulation of PPARγ.

Construction and expression of recombinant fusion protein of thioredoxin-ApoO / 中南大学学报(医学版)

Objective To construct human apolipoprotein O (apolipoprotein O, ApoO) expression vector and obtain recombinant fusion protein thioredoxin (Trx)-ApoO by pET prokaryotic expression system. Methods The ApoO gene fragment from the human liver cDNA library was amplified by PCR. The resulting product was cloned into pET-32a(+) vector and sequenced. The confirmed cDNA was cloned into plasmid E.coli DH10B and then transformed into E.coli BL 21 (DE3) where it was induced to express protein by isopropyl β-D-1-thiogalactopyranoside (IPTG).The fusion protein was purified by Ni-NTA resin. Results The ApoO gene was cloned by PCR and a 519 bp DNA fragment was shown on the agarose electrophoresis. The cloned gene was sequenced and demonstrated to have the same sequence as that of human ApoO gene in GenBank which justified a successful construction of recombinant plasmid. ApoO cDNA gene fragment was induced by IPTG, and a 34 kD recombinant fusion protein Trx-ApoO was tested on sodium dodecyl sulfate polyacrylamide (SDS-PAGE). Conclusion Human ApoO gene is successfully cloned and its recombinant fusion protein Trx-ApoO is expressed.

Effect of apolipoprotein A-I mimetic peptides on cholesterol efflux in RAW264.7 cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect and possible mechanism of an apolipoprotein (apo) A-I mimetic peptide, D-4F, on cholesterol efflux in RAW264.7 macrophages.@*METHODS@#RAW264.7 macrophages were incubated in the medium containing 8-bromo cAMP (8-Br-cAMP, 0.5 mmol/L) and ox-LDL (50 μg/mL) for 24 h. Then various concentrations of D-4F (0-100 μg/mL) or H89 (20 μmol/L, a protein kinase A inhibitor) were added for the purpose of interference. The intracellular cyclic AMP (cAMP) level was determined by enzyme-linked immunoabsobant assay (ELISA). ATP binding cassette transporter A1 (ABCA1) expression in the macrophages was quantitated by real-time PCR and Western blot.@*RESULTS@#D-4F significantly increased the cholesterol efflux in both concentration and time-dependent manner accompanied by the increase in the intracellular cAMP level, ABCA1 mRNA and protein expression. The effect of D-4F on cholesterol efflux ABCA1 expression was enhanced by 8-Br-cAMP. Although H89 did not affect the basal cholesterol efflux and ABCA1 expression, it could attenuate the effect of 8-Br cAMP.@*CONCLUSION@#D-4F affects cholesterol efflux, cAMP level, and ABCA1 expression in macrophages, which is likely involved in the pathway of cAMP/PKA/ABCA1.

The effects of soluble epoxide hydrolase inhibitors on cholesterol efflux in adipocytes / 中华内科杂志

Objective To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes. Methods 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimilated with 100μg/L LPS after starved for 24 hours, then tAUCB in various concentrations(1 ,10,50,100 μmol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARy) antagonist GW9662 (5 μmol/L).0μmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARγ and adenosine triphosphate binding cassette transporter Al (ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARγand ABCA1 in cells were detected by Western blot, the efflux rates of 3H-cholesterol in cells were detected by means of liquid scintillation counter. Results tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10,50,100 μmol/L tAUCB, cholesterol efflux rates were (5.93±0.66) %, (7.40 ± 0. 43) %, (8. 30 ±0. 34)% ,(9.77±0.42)% respectively, there were significant difference after treated by 10-100 μmol/L tAUCB compared with control(5.67±0.17)%(P＜0.05). With the concentration of tAUCB increased,ABCA1, PPAR mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARγ and ABCA1 in adipocytes. Conclusions tAUCB could up-regulate PPARγ expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.

High fat diet influence on vitamin D receptor expression and endothelial nitric oxide synthase in apolipoprotein E-deficient mice / 中国医师杂志

Objective This study investigated high fat diet influence on the changes of vitamin D receptor (VDR) expression and endothelial nitric oxide synthase (eNOS) in apolipoprotein E-deficient(apoE-/-) mice.MethodsApoE-/- mice and C57BLP6J mice were divide into two groups (normal control and high fat diet),high fat diet group were feed high fat feedstuff.Plasma 25-(OH)D levels were determined by competitive protein binding radioimmunity,VDR expression were determined by immunofluorescence and reverse transcription-polymerase chain reaction.The levels of NO and eNOS were determined by nitrate reductase.ResultsCompared with normal control group,high fat diet caused more severe dam-age of atherosclerosis in wild type mice and apoE-/- mice.In apoE-/- mice,the levels of plasma 25-(OH)D were significantly decreased [(26.44±1.28) ng/mL,(22.68±2.07)ng/mL,(17.46±2.22)ng/mL,(15.88±0.97)ng/mL,P＜0.01],the expression of VDR protein and mRNA were significantly increased[VDR :0.244±0.088,0.346±0.132,0.547±0.128,0.768±0.162;VDRmRNA:0.228±0.083,0.375±0.103,0.451±0.117,0.597±0.131,P＜0.01],and the levels of NO and eNOS were significantly increased[NO:(39.74±4.81)μmol/L,(48.1±5.24 )μmol/L,(67.34±6.14 )μmol/L,(86.74±8.05)μmol/L;eNOS:(8.6±0.77 )U/L,(12.28±1.42)U/L,(15.96±0.92)U/L,(18.68±1.15)U/L,P＜0.01].These changes were more significantly in high fat diet group(P＜0.01).ConclusionsThere were abnormalities of plasma 25-(OH)D level,VDR expression and the level of NO and eNOS in apoE-/- mice.These changes were more significantly in high fat diet group.

Cognitive Emotion Regulation Questionnaire in hypertensive patients / 中南大学学报(医学版)

Objective To examine the reliability,validity,and practicability of Cognitive Emotion Regulation Questionnaire (CERQ) in hypertensive patients in China.Methods Altogether 434 hypertensive patients and 462 healthy subjects were recruited. All the subjects were assessed with the CERQ-Chinese version (CERQ-C), Dysfunctional Attitude Scale (DAS), Mood and Anxiety Symptom Questionnaire-Short Form (MASQ-SF), and Center for Epidemiologic Studies Depression Scale (CES-D). We calculated the mean inter-item correlations for the total CERQ and for each of the subscales. Cronbach's alpha coefficient was used to analyze the inter-correlation and reliability, and confirmatory factor analysis was used to examine the 9-factor model. Results 1) Hypertension group reported significantly higher score than that of healthy ones on rumination (12.19±2.51 vs. 11.51±2.60, P<0.001), catastrophizing(8.82±2.19 vs.8.11±2.70,P<0.001),and blaming others(10.76±2.11 vs. 9.88±2.48,P<0.001), and had significantly lower score than that of healthy ones on positive reappraisal(13.80±3.55 vs.14.71±4.11,P<0.001).2)Reliability:In the hypertension group the Cronbach's alpha for the total CERQ was 0.80, and that for the 9 subscales ranged from 0.71 (self-blame) to 0.90 (rumination). In the healthy group the Cronbach's alpha for the total CERQ was 0.79, and that for the 9 subscales ranged from 0.71 (positive reappraisal) to 0.90 (rumination). The mean inter-item correlation coefficient for the 9 subscales was 0.21-0.42(the hypertension group)/0.19-0.32 (the healthy group). In the hypertension group,the test-retest reliability of the total scale was 0.82, the test-retest reliability of the 9 subscales ranged from 0.73 to 0.92. The confirmatory factor analysis showed that the 9 first-order factor data fitted both 2 samples well. Conclusion CERQ meets the psychometric standard and it is reliable and valid for cognitive emotion regulation strategies, which may be regarded as an appropriate assessment tool.

The status and prospects of niacin and its combination therapy with statins / 中国药理学通报

Niacin, a broad-spectrum lipid-regulating agent, can significantly lower plasma triglyceride and raise the high density lipoprotein-cholesterol.Extended-release niacin added to statins monotherapy could further modify the lipid profile and reduce residual cardiovascular risk.This combination therapy provides a safe, effective and economical treatment for clinicians and may be superior to other drugs combined with statins.

A comparative study of the efficacy and safety Zhibitai and atorvastatin / 中华内科杂志

Objective To compare the lipid lowing effect and the clinical safety between intensive therapy with Chinese medicine Zhihitai and atorvastntin in patients with moderate and high risk of atherosclerosis. Methods All the patients were randomly divided in to a Zhibitai group (n = 85) receiving 480 mg of Zhibitai orally twice a day or an atorvastatin group (n = 84) receiving 10 mg atorvastatin orally once daily. Blood lipoproteins, myocardial enzymes, fiver and renal function were measured before treatment and at the fourth and eighth week after therapy , while high sensitive creactive protein (hs-CRP), P-selectin, matrix-metall proteinase-9 (MMP-9) and soluble intercellular adhering molecule-1 (SICAM-1) were detected before treatment and eighth week after therapy in all patients. Results TC and LDL-C were significantly decreased while HDL-C was increased in both groups after 4 and 8 weeks treatment (P < 0. 05). TG was decreased in Zhibitai group after 4 and 8 weeks of treatment, but it was decreased in atorvastatin group only after 8 weeks of treatment. Inflammatory factors such as hs-CRP, P-selectin, MMP-9, SICAM-1 were decreased significantly (all P < 0. 01), but there was no significant difference between the two groups. There were no difference in liver and kidney function, myocardial enzymes and incidence of muscle-ache and digestive system side reaction. ConclusionsBesides the lipoprotein disorder, inflammatory factors in patients with moderate and high risk of atherosclerosis could be regulated with intensive therapy of Zhibitai. Most importantly, it is safe to use Zhibitai clinically.

Effect of soluble epoxide hydrolase inhibitor on the function of endothelial progenitor cells in patients with coronary heart disease / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of soluble epoxide hydrolase inhibitor (sEHi) tAUCB on the function of endothelial progenitor cells (EPCs) and expression of vascular endothelial growth factor (VEGF) in EPCs in patients with coronary heart disease (CHD).@*METHODS@#Mononuclear cells, from the peripheral blood of CHD patients, were isolated by ficoll density gradient centrifugation and cultured. After 7 days of culture in vitro, EPCs were identified by double staining and flow cytometry. EPCs were then stimulated by 0, 10(-6), 10(-5), and 10(-4) mol/L of tAUCB for 24 h. Migration assay was performed in transwell chamber and tube formation assay was performed by Matrigel-Matrix in vitro model. The expression of VEGF in EPCs was measured by Western blot. EPCs from age and gender matched healthy subjects were also cultured as controls.@*RESULTS@#The migration and tube formation activities of EPCs from CHD patients were obviously damaged compared with those from healthy controls (P<0.05). The tAUCB could dose-dependently increase the migration and tube formation activities and increase the expression of VEGF in EPCs compared with those from CHD patients without treatment. The 10(-6) mol/L tAUCB increased those activities of EPCs and the expression of VEGF with statistical difference.@*CONCLUSION@#sEHi can positively modulate the function of EPCs from CHD patients, suggesting the potential predictive significance of sEHi in the therapy of CHD.

Relationship between B-type natriuretic peptide and outcome of non-cardiac critically ill elderly patients in emergency intensive care unit / 中华老年医学杂志

Objective To explore the prognostic value of B-type natriuretic peptide (BNP) for 28-day mortality of elderly patients with non-cardiac critical ill in emergency intensive care unit (EICU). Methods A total of 70 elderly non-cardiac critically ill patients (age≥60 years) in EICU were enrolled, and the blood samples were collected to detect BNP level after the patients' admission to EICU. After 28 days, the mortality was assessed. Results Twenty-two patients (31.4 %) died during 28 days observation, whose BNP levels were significantly higher than that of the survivors [ln BNP: (6.4 ± 1.2) ng/L vs. ( 5. 1 ± 1.5 ) ng/L, P＜ 0. 05] ; BNP level had an area under the receiver operating characteristic curve of 0. 759 (95% CI: 0. 636-0. 882, P＜0.05) for predicting mortality,and the optimal cut point of BNP was 342 ng/L (sensitivity 77.3%, specificity 68.7%).Conclusions BNP level could be a predictor for 28-days mortality for elderly non-cardiac critically ill patients.

Effects and mechanism of simvastatin and fenofibrate on the expression of hepatic apolipoprotein M in mice / 中国医师杂志

Objective To examine the effects and mechanisms of simvastatin and fenofibrate, and combination of the two drugs on the expression of apolipoprotein M (apoM). Methods The male C57BL/6N mice ( n =32) were random divided into four groups, including control group (with no special treatment), statin group (with simvastatin [10mg/( kg · d) for 4 weeks], fibrate group (with fenofibrate [100mg/( kg · d) for 4 weeks] and combination group ( with simvastatin [10mg/( kg· d)] and fenofibrate [100mg/( kg · d) for 4 weeks]. The levels of apoMmRNA and protein, hepatic nuclear factor (HNF-1α)mRNA, liver X receptor-α (LXRα) mRNA in mouse liver were measured. Results Both of simvastatin and fenofibrate can increase the expression of apolipoprotein M ( 1.97 ± 0. 04,2. 02 ± 0. 02 ) and HNF-1αmRNA ( 1.74 ± 0. 05,1.71 ± 0. 04). Combination group obtained more effects than either single agent ( P ＜ 0. 05 ). Simvastatin could decrease the expression of LXRα mRNA ( 1.00 ± 0. 02 ) ( P ＜ 0. 05 ). Fenofibrate could increase the expression of LXRα mRNA(2. 80 ±0. 04) ( P ＜0. 05). No significant difference in LXRα expression was seen between combination( 1.56 ±0. 03 ) and control group( 1.53 ±0. 03 )( P ＞0. 05). Conclusions Simvastatin and fenofibrate can increase apoM expression. Treatment with combination of the two drugs is more effective, and the mechanism might be related to the regulation of HNF-1α and LXRα.

Investigation of platelet activating factor (PAF) in acute myocardial infarction / 中华急诊医学杂志

Objective To investigate the level of platelet activating factor (PAF) in acute myocardial infarction (AMI) in minipig model and patients, and to study the relationship between PAF and lethal arrhythmia referring to ventricular fibrillation and ventricular tachycardia. Method ( 1 ) The levels of PAF in minipig models ( n = 20) were measured by using ELISA before and 1h after occlusion of left anterior descending coronary artery with balloon at the junction of 1/3 middle and distal portion. The lethal arrythmia was recorded by using electrocardiography. (2) In patients with AMI (n = 72), the levels of PAF were measured on arrival, and 24 h,48 h and 72 h later. The lethal arrythmia, acute heart failure and cardiogenic shock were documented. Results ( 1 ) In minipigs with occlusion of coronary artery for one hour, the mean level of PAF increased from (4.66± 2.89)ng/mL to (6.00±2.82) ng/mL,and thus the increment in PAF was (1 .34± 1.40) ng/mL (P ＜ 0.05). In 13 minipigs with lethal anythmia after occlusion of coronary artery for one hour, the increment in mean level of PAF was ( 1.92 ± 1 .34) ng/mL, whereas the increment in mean level of PAF in other 7 minipigs without lethal arrythmia after occlusion of coronary artery for one hour was as low as (0.28 ± 0. 74 ) ng/mL ( P ＜ 0. 05 ). ( 2 ) In patients, the mean levels of PAF on arrival, 24 h,48 h,and 72 hous after admission were (0.47 ± 0.05) ng/mL,(2.38±0.12) ng/mL,(3.65±0.15) ng/mL and (3.02±0.10) ng/mL, respectively. Of 72 ACI patients, 40 (55%) had complication of lethal arrythnia, heart failure or cardiogenic shock and their mean level of PAF 48 h after admission was (4.72 ± 0.16) ng/mL, whereas mean level of PAF in other 32 (44.44%) without complications was (2.31 ±0.03) ng/mL ( P ＜0.05). Conclusions The level of PAF increased after acute myocardial infarction, and the minipigs and AMI patients complicated with lethal arrythmia had higher levels of PAF.

Preparation of apolipoprotein M monoantibody and its preliminary application / 中华检验医学杂志

Objective To prepare anti-apoM monoantibodies with high affinity and high purity, and investigate apoM distribution among human tissues and different groups of people. Methods BALB/c mice were injected intracutaneously with recombinant apoM. After cytomixis, screening and cloning, we established a hybridoma, which grew well and steadily secreted antibodies. The ascites were acquired by injecting BALB/c mice intraperitoneally and anti-apoM monoantibodies were gained using standard techniques. We detected apoM levels in healthy individuals and the patients with coronary heart disease including stable angina (SA) group and acute coronary syndrome (ACS) group using the anti-apoM monoantibodies. ResultsThree anti-apoM monoantibodies were collected and confirmed after subtype identification and block test. The apoM protein were detected in some human cells and human tissues by these three monoantibodies. The concentration of apoM was (11.02 ±1.96) ×10 -3 g/L, (10. 76± 1.32) ×10-3 g/L, (12. 83 ± 2. 28) × 10-3 g/L in SA, ACS and control group respectively. There was significant difference within the three groups (F = 11. 544, P ＜ 0. 05). Comparing apoM concentrations among control group and coronary heart disease groups, it showed that the levels of apoM were lower in coronary heart disease groups than in control group(t =2. 962 and 3. 967,P ＜0. 05). There was no significant difference between two coronary heart disease groups (t = 1. 033, P ＞ 0. 05). Conclusion Anti-apoM monoantibodies are successfully raised and could combine with apoM in human cells and tissues. This lays the foundation for the apoM study in apolipoprotein metabolism.

Effect of high-density lipoprotein on interleukin-8 secretion in 3T3-L1 adipocytes / 中华内分泌代谢杂志

3T3-L1 adipocytes were cultured with various concentrations of high-density lipoprotein ( HDL, 0, 10, 50, and 100 μg/ml ) for 16 h and with lipopolysaccharide ( LPS, 100 ng/ml ) for another 6 h. Interleukin-8 in the medium was determined by ELISA, and PPAR-γ mRNA expression by reverse transacription polymerase chain reaction (RT-PCR). Interleukin-8 levels were increased in LPS-treated cells ( P＜0.05 ), but decreased in HDL-treated cells in the dose-dependent manner. PPARγ mRNA expressions were increased in HDL-treated groups than those treated only with LPS. These results suggested HDL may decrease interleukin-8 secretion via up-regulating PPARγ expression in adipocytes.

Diagnostic value of pentraxins-3 and triglyceride/high-density lipoprotein cholesterol in acute coronary syndrome / 中国医师进修杂志

Objective To investigate the value of serum pentraxins-3 (PTX-3) together with triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) as predictor risk factors of future acute coronary syndrome(ACS). Methods One hundred and seventy-one cases of selective coronary angiography from July 2008 to December 2009 were collected and analyzed. According to the situation on admission and coronary angiography, patients were divided into three groups: normal control group (25 cases), stable angina pectoris (SAP) group (23 cases) and ACS group (123 cases). Fasting venous blood was extracted for measuring serum PTX-3 and lipids (TG, HDL-C) in the next morning, and the statistical significanc was analyzed. Results The level of serum PTX-3 and the ratio of TG to HDL-C in ACS group [(6.39 ± 3.01)μ g/L, 2.38 ± 2.00] were significantly higher than those in SAP group[(3.87 ± 2.05 ) μ g/L, 1.70 ± 1.01] and normal control group [(2.90 ± 1.94)μg/L,0.95 ±0.35] (P ＜0.01 or ＜0.05). Conclusion Increased serum PTX-3 levels and ratio of TG to HDL-C in patients are closely related with ACS, both of which increase the accuracy of early diagnosis of ACS.