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Objective@#To investigate the effect and mechanism of proprotein convertase subtilisin type 9 (PCSK9) on lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediated oxidized low-density lipoprotein (ox-LDL) uptake by mononuclear macrophage (THP-1) derived macrophages.@*Methods@#THP-1 monocyte was incubated with PMA for 48 hours to induce the differentiation into macrophages. Macrophages were pretreated with human recombinant PCSK9 protein for 1 hour and incubated with ox-LDL for 24 hours to induce foam cells. Oil red O staining was used to observe the accumulation of lipid in the control group (foam cells) and groups treated with different concentrations of recombinant PCSK9 protein, and the intracellular cholesterol content was measured by enzyme method, and mRNA and protein expressions of LOX-1 were detected by real-time PCR and Western blot. The uptake of Dil-labeled oxidized low density lipoprotein (Dil-ox-LDL) was observed by fluorescence microscopy in control group (macrophage), PCSK9 protein treated group and PCSK9 protein plus anti-LOX-1 antibody and IgG antibody treated group. mRNA and protein expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2) were detected in control and PCSK9 protein treated group in the absence and presence of TLR4 inhibitor (TAK-242), NF-κB inhibitor (PDTC). In addition, reactive oxygen species (ROS) production was evaluated in the absence or presence of COX-2 inhibitor (NS-398) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (DPI). The mRNA and protein expression of LOX-1 in the control group (PCSK9 protein pretreated foam cells) and PCSK9 protein group in the absence or presence of TAK-242, PDTC, NS-398 and DPI respectively.@*Results@#(1) The total optical density of intracellular lipid droplets, total cholesterol level, cholesterol ester level and cholesterol ester/total cholesterol ratio as well as expression of LOX-1 were significantly higher in PCSK9 group than those in control group (all P<0.05). (2) The fluorescence intensity of Dil-ox-LDL was significantly higher in PCSK9 group and PCSK9+IgG antibody group than in the control group (all P<0.05). The fluorescence intensity was significantly lower in PCSK9+anti-LOX-1 antibody group than in PCSK9 group and PCSK9+IgG antibody group (all P<0.05). (3) The expressions of TLR4, NF-κB and COX-2 were significantly higher in PCSK9 group than in control group (all P<0.05). The expressions of TLR4, NF-κB and COX-2 were significantly lower in PCSK9+TAK-242 group and PCSK9+PDTC group than in PCSK9 group (all P<0.05). The ROS level was significantly higher in PCSK9 group than in the control group (P<0.05). The ROS levels were significantly lower in PCSK9+NS-398 and PCSK9+DPI groups than in PCSK9 group (all P<0.05). (4) The expressions of LOX-1 mRNA and protein were lower in respective PCSK9 protein plus TAK-242, PDTC, NS-398 or DPI group than in PCSK9 protein alone (all P<0.05).@*Conclusion@#PCSK9 may regulate LOX-1 mediated ox-LDL uptake by the THP-1 derived macrophage via TLR4/NF-κB/COX-2/ROS pathway.
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Objective To explore the influence of collateral circulation on the cognition of persons with severe unilateral carotid artery stenosis or occlusion using transcranial Doppler (TCD) imaging combined with P300.Methods A total of 185 patients with stenosis or occlusion of the carotid artery were enrolled and randomly divided into a monocollateral group (n=83),a multicollateral group (n=79) and a noncollateral group (n=23).The monocollateral group was further divided into an anterior communicating artery (AcoA) group,an ophthalmic artery (OA)group and a post communicating artery (PcoA) group according to their collateral circulation.All patients and 40 normal controls (NC) were tested using the Montreal cognitive assessment (MoCA) and P300,and the correlation between the MoCA and P300 scores was analyzed.Results Compared with the NC group,all the other three groups had significantly lower average MoCA scores and P300 amplitudes.They also had significantly longer average P300 latency periods.Compared with the multicollateral group,both the monocollateral and noncollateral groups had significantly lower average MoCA scores and P300 amplitudes and longer P300 latencies.Comparing the monocollateral group with the noncoilateral group revealed the same trends.Among the monocollateral patients the average MoCA score of the AcoA group was significantly higher than the PcoA and OA group averages,while their average P300 latency period was significantly shorter and the amplitude significantly greater than the PcoA group's average.Correlation analyses showed that the MoCA score was negatively correlated with the P300 latency,but positively correlated with the P300 amplitude.Conclusions Collateral circulation can protect the cognitive function of patients with unilateral stenosis or occlusion of the internal carotid artery to some extent,with multicollateral circulation being more effective than monocollateral and AcoA circulation superior to both PcoA and OA circulation.The MoCA score is significantly correlated with the latency period of P300 in such cases.
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Objective Recent studies show that, tesaglitazar can reduce vascular plaque lipid deposition and inflammatory response in mice.This paper aims to investigate the effects of tesaglitazar, the peroxisome proliferator-activated receptor α/γ( PPARα/γ) agonist on serum lipid, serum nitric oxide ( NO) and heart type inducible nitric oxide synthase ( iNOS) mRNA expression in diabetic mice. Methods Thirty female 3-week-old clean grade mice were fed with ordinary adaptive diet for 7 days.The diabetic mouse model was established by feeding these mice with high-glucose-high-fat diet for four weeks and then taking small doses of streptozotocin( STZ) .These mice were randomly divided into two groups by means of ran-dom number table:control group and tesaglitazar group.Control group continued to be fed with high-glucose-high-fat diet, whereas te-saglitazar group was administered with tesaglitazar orally( high-glucose-high-fat fodder mixed with 20μg/kg tesaglitazar) .After 6 weeks′administration, body weight, total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipo-protein cholesterol(HDL-C) and blood glucose(Glu) levels were measured.Serum NO content were detected with nitrate reductase method, and the expression of iNOS mRNA in heart were detected by RT-PCR. Results Compared with control group[(3.62 ± 0.45)、(2.58 ±0.34)、(1.35 ±0.26)、(19.55 ±3.40) mmol/L], serum levels of TC、TG、LDL-C and Glu in tesaglitazar group [(2.93 ±0.38)、(1.87 ±0.41)、(1.07 ±0.30)、(14.33 ±2.08)mmol/L] were significantly decreased, difference was statistically significant(P<0.01).However, the levels of HDL-C were increased obviously campared with the control group[(1.32 ±0.21) mmol/L vs (1.05 ±0.24)mmol/L, P<0.01];The serum NO content in control group were significantly higher than that in tesaglita-zar group[(75.60 ±8.06)μmol/L vs (41.35 ±5.82)μmol/L] , difference was statistically significant(P<0.01); The ralative quantitative expression of iNOS mRNA in treatment group was significantly lower than that in control group[(0.435 ±0.064) vs (0.568 ±0.067)], difference was statistically significant(P<0.01). Conclusion Tesaglitazar can reduce the production of NO by means of inhibit excessive expressions of iNOS mRNA in diabetic mice.It can also improve the levels of serum lipid, and can delay the progression of atherosclerosis.
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Objective To investigate the changeof plasmadiponectin and N-terminal pro-brain natriuretipeptide (NT-proBNP) levelin the patientwith differentypeof atrial fibrillation (Af) .MethodTwo hundred and thirty-fouresearch sub-jectwere divided into 4 group:sinurhythm group (n= 70) ,paroxysmal Af group (n=52) ,permanenAf group (n=62) and control group (n=50) .The plasmadiponectin level wameasured by the enzyme-linked immunosorbenassay (ELISA) and the NT-proBNP level wadetected by chemiluminescence .4 groupwere comparable in age ,gende,body masindex and basidisea-se.ResultThe NT-proBNP level in the paroxysmal Af group and the permanenAf group wasignificantly increased compared with the sinurhythm group and the control group ,the difference wastatistically significan(P＜0 .05) ,buthe difference be-tween the sinurhythm group and the control group had no statistical significance (P＞0 .05) .The NT-proBNP level in the perma-nenAf group wasignificantly increased compared with the paroxysmal Af group (P＜0 .05) .Compared with control group ,the adiponectin level in the sinurhythm group wasignificantly decreased (P＜0 .05) ,which in the paroxysmal Af group and the per-manenAf group wasignificantly increased compared with the sinurhythm group and the control group ,the difference wastatis-tically significan(P＜0 .05) .The adiponectin level in the permanenAf group wasignificantly increased compared with the parox-ysmal Af group (P＜0 .05) .Conclusion The adiponectin level could be related with the repeated occurrence of permanen Af .
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Objective To investigate the relationship between the polymorphism of adiponectin -11 ,377C> G gene and the risk of coronary heart disease(CHD). Methods A total of 126 CHD patients and 130 healthy controls were enrolled and the frequency of each genotypes and allele gene of adiponectin -11 ,377C > G were detected by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Results (1) The adiponectin gene -11,377C > G sites existed gene polymorphism and the three genotypes were GG, CG and CC. (2) There was statistical difference between CHD group and control group; The G allele frequency of CHD group was significantly higher than that in control group (P G between acute coronary syndrome (ACS) group and stable angina group . ( 4 ) The risk of CHD were increased in CHD patients with G allele gene of adiponectin-11,377C > G (P G is associated with the increased risk of CHD. The increased G allele gene frequency may represent the increased risk of CHD.
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Objective To examine clinical significance and relativity of heart-type fatty acid binding protein (H-FABP) and high-sensitivity C-reactive protein (hs-CRP) in patients with chronic heart failure. Methods Ser-um concentrations of H-FABP and hs-CRP were measured in 60 patients with chronic heart failure and 30 control subjects. Left ventricular ejection fraction (LVEF) was examined by Doppler echocardio graphic in all subjects. Re-sults Serum concentrations of H-FABP and hs-CRP were higher in patients with chronic heart failure than in con-trol subjects[(6.11±1.49)μg/L vs (4.24±1.40)μg/L,and (12.77±3.65)mg/L vs(4.85±1.35) mg/L,t=5.746 and 7.543,P<0.01] but LVEF was lower in patients with chronic heart failure than in control subjects [(42.13±6.55) % vs (61.50±3.89) %,t=-14.902,P<0.01]. In CHF subgroups,H-FABP and hs-CRP lev-el increased with advancing NYHA class (F=26.288 and 351.784,P<0.01) but LVEF decreased (F=252.834,P<0.01). The serum H-FABP concentrations had a positive correlation with serum hs-CRP concentrations (r=0.801,P<0.01),and a negative correlation with LVEF (r=-0.718,P<0.01) ;serum hs-CRP concentrations had a negative correlation with LVEF(r=-0.881,P<0.01). Conclusion Serum H-FABP and hs-CRP levels are in-creased with the worsening of CHF. H-FABP and hs-CRP level are pnsitiviely related. The quantitative determination of serum concentrations of H-FABP and hs-CRP is valuable for risk stratification in patients with chronic heart fail-ure.
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Objective To explore the correlation between serum concentrations of apolipoprotein (Apo) AV and adiponecfin in patients with coronary heart disease (CHD). Method The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) , ApoA I and ApoB were examined in 99 subjects by biochemistry department. Enzyme-linked immunosorbent assay (ELISA) method was used to determine ApoA V and adiponectin. All subjects were divided into CHD group(59 patients) and control group(40 patients). Results The concentration of TG was significantly higher than that in control group [(1.79±1.28) mmol/L vs (1.27±0.79) mmol/L]. The concentrations of HDL-C, ApoA V and adiponectin in CHD group were signifi-cantly lower than those in control group[(1.17±0.25) mmol/L vs (1.29±0.26) mmol/L, (186.71±78.20) μg/L vs (250.29±110.38)μg/L, and (3.81±0.15)mg/L vs (5.33±0.37) mg/L,P<0.05or <0.01]. Serum ApoA V was negatively correlated with TG (r =-0.208, P = 0.040), but positively correlated with HDL-C (r = 0.241, P= 0.016) and adiponectin (r = 0.238, P= 0.018). Conclusions The patients with CHD have decreased serum levels of ApoA V and adiponectin, but increased levels of TG. ApoA V and adiponectin influence the development of CHD.
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Objective To study the relationship between severity of coronary artery lesion and serum level of apolipoprotein A5 (ApoA5). Methods The level of serum total cholesterol (TC), triglyceride (TG), high-den-sity lipoprotein cholesterol (HDL-C ), low density lipoprotein cholesterol (LDL-C ), apolipoprotein A1 ( APOA1), apolipoprotein B (APOB) ,Lipoprotein(a) and uric acid(UA) were examined in 114 patients with coronary heart disease(CHD) and 40 healthy control subjects;Enzyme-linked immunosorbent assay (ELISA) methods was used to determine APOA5. The eoronay heart disease patients were divided into tree groups by the severity of coronary artery lesion: that is one, two and three vessel lesion. Results Compared with control group, APOA5, ApoA1, HDL-C lev-el of CHD groups were lower(P <0.01 or P<0.05) ,TG ,LP(a)and UA were higher(P <0.01 or P <0.05) ,the difference of TC, LDL-C and APOB were not significant (P>0.05 ). In the subgroups of CHD patients, The serum APOA5 concentrations were signficant different between the CHD patients and control group( F=18.605 ,P<0.01 ). Along with the severity of coronary artery,the level of ApoA5 concentrations had a lower trend. The level of ApoA5 was negatively correlated with serum TG level ( r=-0.208, P=0.040) and LP (a) ( r=-0.088, P <0.001). The level of APOA5 had a positive correlation with the serum HDL-C (r= 0.241, P = 0.016). Conclusion There is negative correlation between severity of coronary artery lesion and serum level of ApoA5. The decrease of ApoA5 maybe a risk factor.
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Objective To explore the value of heart-type fatty acid-binding protein (H-FABP) in the early diagnosis of acute myocardial infarction (AMI). Methods Sixty confirmed AMI patients were observed, the data of H-FABP, cardiac troponin T (cTnT), creatine kinase MB (CK-MB) were detected in < 6 h and 6-12 h after the symptoms appeared, and the sensitivity of the three markers was calculated. The specificity was compared with 15 uncertain AMI patients and 45 healthy subjects. Results The early diagnosis sensitivity of H-FABP in < 6 h was 94% in AMI, which was higher than that of cTnT (50%) and CK-MB (56%) (P < 0.05 ). The diagnosis sensitivity of H-FABP, CTnT, CK-MB in 6-12 h was 100%, 92%, 92% respectively (P> 0.05 ). There was no significant difference in the specificity among the three markers (P > 0.05). Conclusions H-FABP has more sensitivity and specificity in the early diagnosis of AMI. It is applicable in the screening of patients who suffered chest pain and the diagnosis of early AMI.