Abstract:Aim To investigate the effects of 1-o-acetylbritannilactone (ABL) isolated from Inula Britannica-F on activation of nuclear factor-κB (NF-κB) and cyclo-oxygenase-2 (COX-2) and intercellular adhesion molecule-1(ICAM-1) expression in human vascular endothelial cells (ECV304) treated with lipopolysaccharide (LPS). Methods ICAM-1 and nuclear P65 in protein extracts from ECV304 cells were detected by Western blotting. COX-2 mRNA was assayed by reverse transcription-polymerase chain reaction(RT-PCR). Results After ECV304 cells were incubated with 12.5, 25, 50 μmol/L ABL for 1 h, COX-2 mRNA level in ECV304 cells treated with LPS was reduced by 35.85%, 42.46% and 53.46%, respectively. Expression of ICAM-1 was decreased by 9.77%, 40.87% and 46.83%, respectively, compared with control group. ABL could antagonize the nuclear translocation of P65, and the increase in nuclear P65 induced by LPS no longer occurred following treatment with ABL. Conclusions ABL inhibits COX-2 and ICAM-1 expression in vascular endothelial cells by inhibiting NF-κB activation.

Abstract:Aim To observe the effect of oxidative stress on nucleolar impairment in C₂C₁₂ and clarify the possible molecular mechanism. Methods 0.5 mmol/L peroxide hydrogen (H 2O 2) were added into the cultured C₂C₁₂ cell lines to mimic oxidative stress. Toluidine Blue staining and total protein synthesis analysis were performed to assess H 2O 2-induced nucleolar structural and functional injury respectively. Immunoblotting and antisense oligonucleotide were used to detect the changes of nucleolar protein nucleolin (also named C23). Results Toluidine Blue staining showed predominantly compact, centrally localized nucleoli in intact control cells, but in H 2O 2-treated cells, an early onset of nucleolar segregation could be found after 3 h and 6 h. Total protein synthesis analysis revealed that compared with normal cells, the capability of cellular protein synthesis is significantly decreased after 6 h treatment with H 2O 2 (p<0.05), and lasted for 24 h. Moreover, an 80 kDa band of nucleolin was found by using immunoblotting after 1 h treatment with H 2O 2, and accompanied by down-regulation of its primary 110 kDa band. The 110 kDa band decreased remarkably after 6 h and 12 h treatment with H 2O 2. After transfected nucleolin antisense oligonucleotides for 24 h and 48 h, expression of nucleolin was down- regulated significantly, and nucleolar segregation and inhibition of total protein synthesis could be observed. Conclusion The molecular mechanism of oxidative stress-mediated nucleolar impairment is related to cleavage and down-regulation of intact nucleolin.

Abstract:Aim The expressive system of low density lipoprotein(LDL) receptor gene was established in the oocyte of the Xenopus laevis and the system is applied to investigation of lowering-lipids and anti-atheriosclerosis. Methods The fluorescence on the membrane with DiI-LDL were determined by culturing the oocytes in the period V and VI so as to judge whether the endogenous LDL receptor in oocyte of xenopus laevis existed. After then the p3.7LDL (an expression plasmid which contain human LDL receptor gene) was transmit to the nucleus of oocyte and the immunofluorescence and immunity colloid golden in the cell membrane were observed under microscope. Results The experiments proved there was no endogenous LDL receptor on the membrane of oocytes in the period V and VI. The exogenous LDL receptor can be expressed after the p3.7LDL was transmitted to the nucleus of oocyte. Conclusion Human LDL receptor gene can be expressed in Oocyte of Xenopus laevis and the system can be used in the investigation of lowering-lipids and anti-atheriosclerosis.

Abstract:Aim To investigate the effect of platelet activating factor receptor (PAFR) antagonist on angiogenesis in plaque and lesion area of apolipoprotein E-deficient mice (apo E -/-). Methods 8-week-old male apo E -/- mice were fed a standard chow diet for 24 weeks to develop advanced lesions. Mice were then separated into the following two groups (n=18) and treated for 8 weeks: (1) chow diet with regular water, (2) chow diet with WEB₂086 in the water (4.3 mg in 100 mL). Whole-Mount CD31 Stain and Plaque-Associated Sprouting have been used to estimate angiogenesis in plaque of aorta, Sudan Ⅳ staining to measure lesion area. Results Administration of WEB 2086 did not affect the lipid composition of mouse serum. However, lesion area was r significantly educed (31.4%±9.7% vs 17.5%±6.3%,p<0.01). The mean density of intimal capillarie of atherosclerotic plaque (34.6%±10.2% vs 16.1%±6.7%,p<0.01) and the mean number of sprouts per ring were significantly reduced in the WEB₂086 group (172.3±40.6 vs 73.1±24.9,p<0.05). Conclusions These studies provide evidence that WEB₂086 can inhibits angiogenesis in atherosclerotic plaque and reduce lesion area of apolipoprotein E-deficient mice.

Abstract:Aim To construct recombinant adeno-associated viruses (rAAV) vectors carrying human apolipoprotein A_Ⅰ (apoA_Ⅰ) and apo A_Ⅰ Milano cDNA, and explore a new strategy to prevent and treat the atherosclerotic diseases. Methods Human apo A_Ⅰ cDNA with a his-tag in upward of the cDNA sequence was obtained by reverse transcription-polymerase chain reaction (RT-PCR) and polymerase chain reaction (PCR), human apo A_Ⅰ Milano cDNA was then prepared by Site-Directed Mutagenesis. The particle numbers of rAAV vectors after extractd with a most economic and convenient method was assayed by Dot-blot, and the purity was assayed by SDS polyacrylamide gel electrophoresis (SDS-PAGE). The expression efficiency of the apo A_Ⅰ and apo A_Ⅰ Milano in C₂C₁₂ after infected by rAAV vectors were detected by ELISA method. Results The titre of the rAAV vectors of apo A_Ⅰ and apo A_Ⅰ Milano was about 2×10 14/L, and the result of SDS-PAGE showed the purity of the rAAV vectors was good. The expressed apo A_Ⅰ level is 0.39±0.04 mg/L and the apo A_Ⅰ Milano is 0.31±0.03 mg/L in the DMEM culture medium. Conclusions The success of the rAAV vectors construction and purification and the expression of apo A_Ⅰ and apo A_Ⅰ Milano in C2C 12 cells mediated by these vectors, makes the injection of rAAV encoding human apo A_Ⅰ (rAAVA) and rAAV encoding human apo A_Ⅰ milano (rAAVAM) vectors in mouse muscular cells possible, and contributes to the hope of finding a safe and effective way to prevent and treat atherosclerotic diseases.

Abstract:Aim To learn the effects of advanced glycation end products (AGE) on expression of scavenger receptor BI (SR-BI)in U937 macrophages. Methods U937 macrophages differentiated for 48 h were incubated with AGE. Immunocytochemical method and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect SR-BI protein and mRNA levels. Results Immunocytochemistry showed that after exposure of U937 macrophages to 100, 200 and 400 mg/L AGE, the average integrated optical density values of SR-BI protein expression were 18.94±3.56, 27.86±4.39 and 35.08±2.37 respectively, significantly higher than that in BSA group (13.76±3.74, p<0.05), the average integrated optical density values of SR-BI protein expression in U937 macrophages following 400 mg/L AGE for 6, 12, 24, 48 h were 16.87±5. 65, 25.68±6.97, 35.08±8.37 and 39.68±9.37, higher than that in 0 h group (12.02±3.47, p<0.05). RT-PCR showed that expression of SR-BI mRNA was 0.32±0.03, 0.53±0.05, 0.64±0.04 and 0.89±0.05 in 400 mg/L BSA, 100, 200 and 400 mg/L AGE groups. SR-BI mRNA expression in U937 macrophages following 400 mg/L AGE for 0, 6, 12, 24, 48 h was 0.41±0.01, 0.62±0.05, 0.80±0.08, 0.87±0.05, 1.24±0.13, respectively. Conclusions U937 macrophages that were incubated in medium containing AGE showed an increase in the expression of SR-BI protein and mRNA in a time- and dose-dependent manner.

Abstract:Aim To study the change of the interleukin-8 (IL-8) content in blood and cerebrum after cerebral ischemia-reperfusion injury. Methods With Zea Longa's thread method, cerebral ischemia-reperfusion injury model of rats was established. The rats were randomly divided into the groups as sham operated control group and ischemia-reperfusion 3 h, 6 h, 12 h, 24 h and 48 h groups. The content of IL-8 in blood serum and brain tissue was detected by double antibody sandwich enzyme-linked immunosorbent assay. Results The content of IL-8 in blood serum was increased significantly at 3 h after reperfusion (p<0.01), and then went down. It reached the level of the control group at 24 h after reperfusion. The concentration of IL-8 in brain tissue was peaked at 6 h after reperfusion (p<0.01), went down after 12 h reperfusion. Moreover, there is no difference between the group of 6 h after reperfusion and 12 h after reperfusion (p>0.05). Conclusion IL-8 was involved in the pathophysiological course of cerebral ischemia-reperfusion injury.

Abstract:Aim To evaluate the effects of Methyl 3β-hydroxy-5α, 6α-epoxycholanate (MHEC) and T-0901317 on the expression of ATP-binding cassette transporter A1 (ABCA1), liver X receptors (LXR)αand LXR β in THP-1 cells. Methods THP-1 cells were cultured and treated with LXRs agonists MHEC and T-0901317 respectively. The mRNA expressions of ABCA1, LXRα and LXRβ were detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to assess the expression of ATP-binding cassette transporter A1 protein in the cells. Results Both of the two LXR agonists' treatment significantly increased ABCA1 mRNA and LXRα mRNA in a time and dose-dependent fashion in THP-1 cells. The expression of ATP-binding cassette transporter A1 protein also increased in the treated cells. While the LXRβ expression in T-0901317 group was stronger than in MHEC group. Conclusions Both MHEC and T-0901317 can up-induce the expressions of ATP-binding cassette transporter A1 and LXRα in THP-1 cells, and MHEC is more likely to be a selective agonist to LXRα.

Abstract:Aim To investigate the effect of Angiotensin-(1-7)[ Ang-(1-7)]on the activities of protein kinase C (PKC), migogen-activated protein kinase (MAPK) and calcineurin (CaN) in cultured rat adventitial fibroblasts to affect proliferation. Methods PKC, MAPK and CaN activities were measured in cultured rat adventitial fibroblasts, the proliferation was examined by 3H-Thymidine (3H-TdR) and 3H-Leucine (3H-Leu) incorporation. Results By contrast, AngⅡ promoted PKC, MAPK and CaN activities in cultured rat adventitial fibroblasts (p<0.01 or p<0.05). Ang-(1-7) not only inhibited PKC, MAPK and CaN activities, but also decreased AngⅡ mediated PKC, MAPK and CaN activities, compared with their respective controls (p<0.01 or p<0.05). AngⅡ increased 3H-TdR and 3H-Leu incorporation in cultured rat adventitial fibroblasts, Ang-(1-7) not only inhibited 3H-TdR and 3H-Leu incorporation, but also decreased 3H-TdR and 3H-Leu incorporation mediated by AngⅡ in cultured rat adventitial fibroblasts, compared with their respective controls (p<0.01 or p<0.05). Conclusion It is concluded that Ang-(1-7) inhibited cultured rat adventitial fibroblasts proliferation by depressing PKC-MAPK and CaN signaling pathway

Abstract:Aim To observe the effects of treatment with celecoxib, a specific cyclooxygenase-2 inhibitor, together with low-dose aspirin on atherosclerosis progression in an apolipoprotein-E knockout (ApoE -/-) mice model. Methods 8-week-old ApoE -/- mice fed on a western-diet were devided into group aspirin (n=10), group aspirin+celecoxib (n=11), and group placebo (n=8). Aspirin, aspirin+celecoxib and placebo were given respectively by oral gavage. Wildtype mice fed on a normal diet were as normal control group (n=6).At 16 weeks of age, serum total cholesterol (TC) and triglyceride (TG) were determined, atherosclerotic lesions in arotic root were evaluated by oil red O staining. Results A small difference in serum TC and TG levels was found either in group aspirin or in group aspirin+celecoxib compared with group placebo (30.2±5.5 mmol/L and 28.6±6.2 mmol/L vs 37.8±8.1 mmol/L,p<0.05, p<0.05); However, there was no significant difference between the two treatment groups. Oil red O staining showed that mean plaque size in arotic root was significant smaller either in group aspirin+celecoxib or in group aspirin compared with group placebo (p<0.01), and it was much smaller in group aspirin+celecoxib (0.042±0.026 mm2 vs 0.068±0.022 mm2, p<0.05). Conclusions Aspirin can slightly decrease serum level of TC in ApoE -/- mice; Celecoxib, together with low dose aspirin, can reduce the progression of atherosclerosis to a much more extent

Abstract:Aim To study the protective effect of trimetazidine (TMZ) on mitochondria of myocardial ischemia and ischemia reperfusion injury and its mechanism. Methods Totally 50 SD rats were randomly divided into 4 groups: the pseudooperation group, the saline group and the TMZ treated groups (5 mg/kg and 10 mg/kg). In the pseudooperation group the coronary artery was not ligated but the chest was opened, the other groups were the model of myocardial ischemia reperfusion injury(RI). The level of malonaldehyole(MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) and the accumulation of Ca 2+ in mitochondria of myocardial were detected at ischemia 30 min and reperfusion 40 min. The myocyte ultrastructure was also observed by electron microscope in 4 groups. Results Compared with the pseudooperation group, the MDA and total Ca 2+ were significantly higher and the SOD, GSH, GSH-Px were significantly lower in saline group and treated groups. Compared with the saline group, the MDA and total Ca 2+ was significantly lower and the SOD, GSH, GSH-Px were significantly higher in treated group. The ultrastructure changes of myocardium ulder electron microscope showed that the damage degree of mitochondria is slighter in TMZ treated groups than in saline group. Conclusions TMZ could significantly reduce the injury of lipid peroxidation of myocardial mitochondrial induced by ischemia and ischemia reperfusion. The mechanism may be that TMZ could increase the content of GSH and the acvitity of SOD and GSH-Px, and enhance its antioxidant production. TMZ could protect the cardiac cells by reducing calcium overload in myocardial mitochondria.

Abstract:Aim To study the protecting effect of Polygoni Multiflori total glycosides(PMTG)on the atherosclerotic lesion formation. Methods Thirty-two female apolipoprotein E gene deficiency mice were randomized into four groups: PMTG high dose group [150 mg/(kg·d)],low dose group [25 mg/(kg·d)],atorvastatin positive control group [5 mg/(kg·d)],and blank control group. At the end of the tenth week, all mice were killed. The serum levels of total cholesterol (TC), Triglyceride (TG), high density lipoprotein cholesterol (HDLC)were measured by enzyme dynamics method. Light microscopy were adopted to assess the degree of As lesions of aortic wall and image analysis was performed with computer. Results As compared with the blank control group, 1.PMTG could reduce the levels of serum TC, TG significantly (TC: 649.3±72.2 mg/dL, 632.6±55.1 mg/dL, 497.4±140.8 mg/dL vs 809.4±42.6 mg/dL, respectively, p<0.01; TG: 126.6±48.1 mg/dL, 145.6±37.9 mg/dL, 172.1±15.7 mg/dL vs 253.3±42.6 mg/dL, respectively, p<0.01); but elevate HDLC level significantly(117.1±14.9 mg/dL, 113.5±23.3 mg/dL, 126.7±12.8 mg/dL vs 67.3±10.6 mg/dL, respectively, p<0.01). There are no differences beween cured groups in the serum level of blood lipids (p>0.05). 2.It could also reduce the extent of atherosclerotic lesion and the aorta plaque areas were significantly lower (3.97%±0.62%, 3.11%±0.01%, 0.86%±0.07% vs 18.50%±6.54%, respectively, p<0.05). Conclusion The resulting data provide the occurrence and the development of atherosclerotic lesions could be inhibited by the PMTG because of its lipid-regulated ability.

Abstract:Aim To evalvate the effects of endovascular irradiation associated with simvastatin and clopidogrel on restenosis after interveneional therapy. Methods 72 male New Zealand white rabbits were studied. Except those in normal control group, other rabbits were made into athetoscletosis and restenosis modles. Immunohistochemistry method was used to detect the data expressed in the vascular. The expression were analyzed by image analysis. All these collected data were analyzed using factorial ANOVA. Results At each time point, the lumem area was larger and the neointima area was smaller in associated group than in other groups(p<0.05). The expression of matrix metalloproteinase-2(MMP-2), proliferation cell nuclear antigen(PCNA), α-SM actin in the vascular in the iliac arteries of associated group is the least (p<0.05). Conclusion 32 P irradiation associated with simvastatin and clopidogrel has the effect of preventing restenosis after balloon injury.

Abstract:Aim To investigate the protective effect of fluvastatin on ischemia reperfusion myocardium in normocholesterolemic rabbit. Methods 24 rabbits were divided into three groups randomly and myocardial ischemia reperfusion model in rabbit was made. Rabbits were subjected to 45 min of regional myocardial ischemia and 3 h of reperfusion. 10 mg/(kg·d) fluvastatin were oral administered for one week. Dynamic index of myocardial function was recorded and analyzed. Serum activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were detected. Infarcted sizes in heart were determined by dual staining with Evans-blue and TTC. The activity of induced nitric oxide sythase (iNOS) and total nitric oxide synthase (tNOS) were detected in ischemic myocardium. Results In comparison with control group, all indexes related to injury, namely left ventricular end-diastolic volume (LVEDP), ±dp/dt max, MB isoenzyme of creatine kinase (CK-MB), LDH-1 and the ratio of myocardial necrosis area, show injury attenuation in fluvastatin group. Increase of activity ratio iNOS/tNOS due to ischemia reperfusion is reduced significantly in fluvastatin group compared with control group (0.25±0.10 vs 0.61±0.13, p<0.01). Conclusion Fluvastatin can attenuate myocardial ischemia reperfusion injury in rabbit. Its protective effect may be assoctiated not only with up-regulation of tNOS but also with modulation of iNOS in myocardium.

Abstract:Aim To investigate the effects of oxidized high density lipoprotein(ox-HDL) on apoptosis and intracellular free calcium concentration (i) of human umbilical endothelial vein cells and to infur its possible mechanism of this ECV304 injure. Methods Ox-HDL was incubated with Cu 2+, and different concentrations of ox-HDL was incubated with endothelim cells. PI staining test was conducted to analyze apoptosis index, and i was determined by fluo-3/AM, the injury of cells was observed by scanning electronic microscopy(SEM). Results High-concentration ox-HDL can induce the injury and apoptosis of ECV304 cells; the level of intracellular free calcium concentration also increase with the increasing concentration of the ox-HDL. In detail, with the prolongation of incubation period, the endothelial injury,apoptosis and intracellular calcium also increased. Conclusions High_concentration ox-HDL showed synergetically injurious effects on endothelial cells, which aggravated the apoptosis and intracellular free calcium concentration of ECV304 cells. This may at least partly attribute to the hypothesis that the increase of intracellular calcium may mediate the apopotosis of the endothelial cells ,which plays a role in the development of atherosclerosis.

Abstract:Aim To observe the role of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinases-2(TIMP-2) on the left ventricular function and extracellular matrix remodeling after acute myocardial infarction. Methods Male SD rats were randomly divided into operator group and sham group, and the model was established by ligation of coronary artery. The left ventricular function (by catheter measuring) were studied at different time. The protein expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 was examined by immunohistochemical analysis and Western-blot. Results Compared with sham group, the left ventricular function deteriorated and ventricular remodeling occurred after acute myocardial infarction. And the protein expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 elevated (p<0.05). Conclusion Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 involved in the left ventricular function deterioration and ventricular remodeling after acute myocardial infarction.

Abstract:Aim To investigate the pathology characteristic of femoral atherosclerosis in elder diabetes patients. Methods 8 elder diabete autopsy cases and 8 control cases were selected respectively in our hospital. Serial sections of femoral artery of all cases were taken. All the arteries were examined, and parts of the segments were selected for immunohistochemical staining. Three markers against α-smooth muscle actin, CD68, and bax were performed. Results Compared with control cases, the femoral atherosclerosis was more serious and the calcify range was wider in diabete patients; there were less smooth muscle cells and more macrophage in femoral atherosclerotic plaques, and the expression of bax in macrophages was stonger, the expression of bax in smooth muscle cell was weaker. Conclusions Diabete may accelerate the occurrence and development of femoral atherosclerosis.

Abstract:Aim To investigate the relationship of plasma homocysteine (Hcy) level and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine β-synthase (CBS) T833C related to homocysteine metabolism with carotid intima-media thickness (IMT) in type 2 diabetic patients. Methods Plasma Hcy level was measured by enzyme linked immunosordent assay (ELISA). MTHFR genetic C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP), and CBS T833C polymorphism was determined by amplification refractory mutation system (ARMS) method, carotid intimal-medial wall thickness was determined by the use of the duplex ultrasonography. Results The genotype frequency of diabetics with thicked IMT was different from that of diabetic patients with normal IMT and control groups (p<0.05). Plama homocysteine levels were markly higher in patients with MTHFR or CBS genetic mutation than those in patients without mutation in each group. IMT in MTHFR or CBS genetic mutation were thicker than those in patients without mutation in diabetic group. Conclusion Mutation of MTHFR or CBS can both cause the elevation of plasma homocysteine level so as to induce the onset of arteriosclosis in diabetics. Their genetic mutations are possibly the important mechanism of macroangiopathy in diabetics.

Abstract:Aim The accumulating evidence suggests that C-reactive protein (CRP) may have direct inflammatory effects on the vascular wall and that statin therapy may have important non-lipid anti-inflammatory effects confirmed by decreasing serum inflammatory markers,such as CRP. However,the effect of pravastatin on tumor necrosis factorα (TNFα) and interleukin-6 (IL-6) release in cultured human monocytes from patients with acute coronary syndrome(ACS) was not investigated. Methods A prospective,human monocyte culture, pravastatin intervention study. Monocytes were isolated from blood of patients with acute coronary syndrome (ACS) and healthy volunteers by the Ficoll density gradient and stimulated by CRP (20 mg/L) or lipopolysaccharide (LPS,10 μg/L) for 24 h. Also 1 μmol/L,5 μmol/L,and 10 μmol/L pravastatin was coincubated with cells in the presence of CRP. Measurements of TNFα and IL-6 were performed from supernatants of cultured medium in duplicate,using a commercial assay kit. Results (1)CRP and LPS induced the release of TNFα and IL-6,with significantly elevated levels in cultured supernatants in ACS group and healthy group compared with their control group respectively.(2)A greater increase of TNFα and IL-6 induced by CRP and LPS were observed in the ACS group compared with the healthy group. Pravastatin inhibited significantly the production of TNFα and IL-6 in monocytes stimulated by CRP in a dose-dependent manner, a greater decrease was observed in ACS group compared with the control group(p<0.001). Conclusions CRP and LPS could induce more TNFα and IL-6 release in human monocyte from patients with ACS than from healthy volunteer. Pravastatin could inhibit this response in a dose-dependent manner in ACS group better than in healthy volunteer,which may provide an insight into the mechanisms of anti-inflammatory actions of pravastatin.

Abstract:Aim To study the relationship between polymorphisms of apolipoprotein E and serum lipid. Methods The multiplex amplification refractory mutation system polymerase chain reaction technique was used to analyze the apolipoprotein E (apo E) genotype of 113 hyperlipoproteinemia patients and 108 healthy controls, as well as serum lipid. The results was processed by the statistical analysis. Results The serum levels of triglyceride, total cholesterol, low density lipoprotein cholesterol in the hyperlipoproteinemia patients were significantly higher than in the healthy controls (p<0.05), however, high density lipoprotein cholesterol and apolipoprotein A_Ⅰ was much lower in hyperlipoproteinemia patients (p<0.05); Among the three genotypes of apolipoprotein E, apolipoprotein E3/3 was the most common one, the apolipoprotein E ε4 allele frequency in the hyperlipoproteinemia patients was much higher than in the healthy controls (p<0.05). Conlusions High density lipoprotein cholesterol was of great importance in reducing serum lipid, and gene polymorphisms of apolipoprotein E may be a genetic factor in hyperlipoproteinemia patients.

Abstract:Aim To investigate the relationship between the levels of pregnancy-associated plasma protein-A (PAPP-A) and high-sensitivity C-reactive protein (hs-CRP) in patients with unstable angina (UA), and the role of PAPP-A in predicting the stability of atherosclerotic plaques. Methods Patients were divided into two groups according to the clinic presentation, one with stable angina pectoris (SA group, n=38) and one with UA (UA group, n=42). The levels of PAPP-A, hs-CRP and other serum biomarkers were measured before coronary angiography; the angiograms were analyzed with Jenkins score. Results The plasma hs-CRP, PAPP-A levels in patients with UA increased significantly, compared with those in SA group (hs-CRP 4.40±0.003 vs 0.48±0.016 mg/L, p<0.001; PAPP-A 18.40±0.002 vs 7.79±0.001 mIU/L, p<0.001); the Jenkins scores of coronary artery angiography in patients with UA increased significantly compared with those in SA group (5.06±0.002 vs 1.94±0.002,p<0.001). PAPP-A was significantly related with hs-CRP (r=0.44); using the method of Multiple Regression and Correlation, PAPP-A had linear relationship with hs-CRP, cardiac troponin I (cTnI) in all of the cases, and Jenkins scores had linear relation with PAPP-A, cTnI and high density lipoprotein cholesterol. Conclusions PAPP-A can play a role in evaluating the clinic stability of the patients with coronary artery disease, and may act as one of the biomarkers of vulnerable plaques.

Abstract:Aim To explore the concentration changes of plasma homocysteine (Hcy) and gene mutation of methylenetetrahydrofolate reductase (MTHFR C677T) different type of coronary heart disease (CHD) and different vessel number of coronary artery where found significant lesion by coronary angiography (CAG), analyse the relationship between gene mutation of MTHFR C677T and the levels of plasma Hcy and the relationship between the gene mutation and CHD. Method The total subjects were divided four groups as follows: 74 patients without coronary heart disease (control group), 32 patients with stable angina pectoris (SA), 104 patients with unstable angina pectoris (UA), 25patients with acute myocardial infarction (AMI),which were all documented by CAG. The plasma Hcy was determined by high-performance liquid choromatography (HPLC) assay and the genotypes of MTHFR C677T were determined by PCR-based assay. Results The mean levels of plasma Hcy in CHD were significantly higher than control group, those in the AMI group and UA group were significantly higher than control group and SA group, those in the patients with single-vessel disease was higher than in non-vessel disease or in 1double-vessel, in triple-vessel disease. The mean levels of plasma Hcy in the patients with mutant homozygote for MTHFR C677T was higher than wild homozygote or heterozygote. The incidence rate of gene mutation of MTHFR C677T in CHD were higher than control group, but there was no statistic significance. Correlation analyses showed the correlation coefficient of MTHFR C677T gene mutation to CHD or plasma Hcy was 0.000, 0.000 respectively. Using binary Logistic regression analysis we found the adjusted odds ratio of moderate hyperhomocysteinemia for CHD was 1.138. Conclusion The high plasma Hcy may be independent risk factors of CHD, furthermore, may be the marker of acute coronary syndrome (ACS), but not have positive correlation with the vessel number of coronary artery where found significant lesion by CAG. Methylenetetrahydrofolate reductase C677T gene mutation is neither an independent risk factor of CHD, nor the most important factor determining the concentration of plasma Hcy.

Abstract:Aim To study clinical relationship of plasma adhesion molecule levels of coronary circulation in patients with acute coronary syndrome (ACS). Methods The plasma intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in the coronary sinus and aortic root were simultaneously examined in 30 patients with ACS, 35 patients with stable angina pectoris (SA) and 27 patients with control subjects. The plasma levels of ICAM-1 and VCAM-1 were measured by enzyme-linked immunosorbent assay. Results Both in the aortic root and the coronary sinus, the plasma ICAM-1 and VCAM-1 levels were significantly higher (p<0.05) in patients with ACS than in those with SA and in control subjects. The different plasma levels of adhesion molecules between coronary sinus and aortic root were significantly higher (p< 0.001) in patients with ACS than in those with SA and in control subjects. There were no significant differences in the values between in the coronary sinus and aortic root in patients with SA and control subjects. There were no significant relationship between plasma ICAM-1 and VCAM-1 levels and coronary lesion degree. Conclusions The plasma ICAM-1 and VCAM-1 levels were significantly higher in ACS. The changes of plasma ICAM-1 and VCAM-1 levels in coronary circulation reflect the severity of inflammation of coronary artery and may be related to plaque unstablity.

Abstract:Aim To evaluate the predictive value of carotid atherosclerosis(CAS) in coronary heart disease(CHD). Methods Carotid ultrasound was performed in 191 CHD patients and 175 normal controls. These patients are divided into4 groups according to the results of angiography. Then intimia-media thickness(IMT) and the degree of carotid atherosclerosis were compared in 4 groups. According to the degree of carotid atherosclerosis, the presence of coronary heart disease will be predicted. Results We found that there were significant differences in intimia-media thickness and prevalence rate of atherosclerotic and narrowness rate of carotid artery between control group and the coronary heart disease groups (p<0.05). The more serious the coronary artery disease, the higher incidence rate of carotid artery atherosclerosis. The positive predictive value of carotid plaque score>1, 2, 3 was 68.5%, 73.2%, 74.6%. Conclusion The carotid atherosclerosis is regarded as a better predicative marker for coronary heart disease. Its extent may reflect directly the occurrence, severity and extent of coronary heart disease.

Abstract:Aim To observe the relationship between carotid atherosclerosis (CAs) and coronary arterial atherosclerosis (CAAs) in patients complicated with diabetes mellitus (DM). Methods Coronary arteriography was performed in 73 patients with diabetes mellitus to judge the degree of CAAs. The carotid intima-media thickness(IMT) and carotid plaques were measured by ultrasound. Results There was significant difference between CAAs group with DM in IMT, carotid plaques score and incidence of carotid atherosclerosis plaques (p<0.001,p<0.005,p<0.01). There was positive correlation between rami of CAAs with DM and IMT, carotid atherosclerosis score (r=0.71,0.68, p<0.001). There was positive correlation between coronary arteriography score and IMT, carotid atherosclerosis score (r=0.69, 0.66, p<0.001). Conclusion There was close relationship between CAs and CAAs in patients of coronary heart disease complicated with diabetes mellitus.