Abstract:Aim To investigate the signaling mechanism of estrogen reducing endoplasmic reticulum stress induced apoptosis, to explore the protective mechanism of the effect on cardiovascular, through establishing the ER stress cell model in human umbilical vein endothelial cell. Methods To establish ERS cell model, HUVECs were incubated in 10 μmol/L tunicamycin (TM) or 2 mmol/L dithiothreitol(DTT) with or without 10-8 mol/L 17β-estradiol(E₂) pretreatment. Tested glucose regulated protein (GRP78) to determine whether the model was successfully established and explored the impact of E₂ in ERS. The changes of three major signaling pathway proteins of ERS were detected by Western blot, and the most significant increase is the most important signal pathway of ERS. To explore the impact of E₂ in apoptosis induced by ERS, the apoptosis protein C/EBP-homologous protein( CHOP) was analyzed by Western blot and the apoptosis rate of cells was tested by Hochest staining. To explore the role of estrogen receptor in its suppression of ERS, we added ICI182780 (ERα, ERβ antagonist and GPER agonist) and G15(GPER antagonist) before adding E₂, and analyzed the expression of the main signal pass of ERS by western blot. Added the inhibitors of E₂ receptor signaling, to explore the main post-receptor signaling pathway. Results The expression of GRP78 was significantly increased in TM/DTT group,and the protein kinase R-like ER kinase(PERK) was the most significant increase one among the three signaling pathways of ERS. In the presence of E₂, the regulations replied. The expression of CHOP and the apoptosis rate of cells were significantly increased in TM/DTT group,and regulations replied when added E₂. The inhibition of E₂ to the up-regulation of p-PERK/PERK was inhibited by ICI182780 and G15 respectively, the blocking is the most obvious while adding both. The effect of E₂ reduced p-PERK/PERK were weakened when added the inhibitors of E₂ receptor signaling respectively,and the weakness was the most obvious when added the signaling inhibitor of Akt. Among them, the effect of PI3K-Akt inhibitor was the most significant. Conclusions E₂ can protect human endothelial cells from ERS induced by TM and DTT. p-PERK/PERK pathway may be the most important signal path of ERS. E₂ plays a role in inhibiting HUVEC apoptosis induced by over ERS. The receptors of E₂ play an important role when E₂ inhibited apoptosis induced by over ERS. The activated E₂ receptor can activate rapid estrogen receptor signaling pathways include PI3K-Akt, ERK1/2, JNK and p38-MAPK to inhibit ERS, and PI3K-Akt pathway may be the most important one. E₂ possibly prevent vascular endothelial cells by inhibition of apoptosis induced by ERS, and the mechanism of inhibiting ERS was mainly through the activated E₂ receptors activating PI3K-Akt pathway.

Abstract:Aim To explore the role of prenatal exposure to lipopolysaccharides (LPS) on blood lipids in offspring rats. Methods Eight pregnant rats were randomly divided into control group and LPS group. The rats in these groups were intraperitoneally administered with vehicle or LPS 0.79 mg/ kg on the 8 th, 10 th and 12 th days, respectively. Liver histopathological alteration was observed by hematoxylin-eosin staining and transmission electron microscopy, 8-OHdG expression was determined by confocal laser-scanning microscope and mitochondrial potential was detected by microplate reader in 8-week-old offsprings. Simultaneously, the body weight was measured in offsprings weekly and at day 1. Results By comparison of those offsprings in control group, body weight of offspring rats in 1 day and 1 week were both significantly decreased (P＜0.01). Whereafter, the body weight of offsprings in LPS group were increased obviously from 2 nd week to 8 th week (P＜0.01). Compared with offsprings from control group, there were dramatic increases in the serum level of TG, TC, LDL and AST (P＜0.05 or P＜0.01). In 8-week-old LPS offsprings, the liver exhibited significant lesions, in particular mitochondrial pathological alterations. The functional analysis of mitochondria suggested the expression of 8-OHdG increased obviously, and the mitochondrial potential decreased significantly in offsprings of LPS group (P＜0.01). Furthermore, the thoracic aortas exhibited lesions, including impaired endothelial cells, and migration and proliferation of vascular smooth muscle cells. Conclusion Our results indicate that maternal LPS exposure during pregnancy leads to mitochondrial dysfunction in offspring that predispose to disorder of blood lipids and even atherosclerosis in adult.

Abstract:Aim To investigate the effect of curcumin in reducing human umbilical vein endothelial cell (HUVEC) injury induced by lipocalin-2 and the possible mechanism. Methods Lipocalin-2 at different concentration (0, 5, 10, 20 μmol/L) and different time gradient (0, 24, 48 and 72 h) were added in HUVEC, CCK-8 assay and flow cytometry were used to detect proliferation and apoptosis of HUVEC, the contents of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in HUVEC supernatant were determined by enzyme-linked immuno-sorbent assay (ELISA), lactic dehydrogenase (LDH) activities were determined by colorimetry, the expressions of p-p38 MAPK, Bax and Bcl-2 in HUVEC supernatant were determined by Western blot. 10 μmol/L curcumin and 25 μmol/L SB203580 were added into HUVEC to detect the effect of curcumin. Results Compared with the control group, lipocalin-2 could significantly restrain the proliferation of HUVEC, increased the apoptosis of HUVEC, the MCP-1, IL-6 contents and LDH activities in HUVEC supernatant and Bax/Bcl-2 rate (P＜0.05). Compared with lipocalin-2 group, curcumin and SB203580 could increase the proliferation of HUVEC, restrained the apoptosis of HUVEC, the MCP-1, IL-6 contents and LDH activities in HUVEC supernatant and Bax/Bcl-2 rate (P＜0.05). Conclusions Our findings indicated that curcumin could reduce HUVEC injury induced by lipocalin-2, the protective mechanism is related to the inhibition of p38 MAPK pathway.

Abstract:Aim To investigate the effect of Na＋/H＋ exchanger-1 (NHE1) inhibitor amiloride on the degradation of apolipoprotein A1 (ApoA1)-induced ATP binding cassette transporter A1 (ABCA1) in the mice macrophages.Methods The peritoneal macrophages were collected from the mice at various indicated time points after intravenous injection of ApoA1. ABCA1 mRNA and protein levels in the macrophages were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Furthermore, the mice intervened with ApoA1 for 8 h were intraperitoneally injected with amiloride or calpain inhibitor ALLN. The treated mice were divided into four groups:control group, amiloride group, ALLN group and amiloride＋ALLN group. ABCA1 protein was detected by Western blot and calpain activity was assessed by fluorescence method in macrophages. Results After mice intervened with ApoA1, ABCA1 mRNA had no obvious change, but the level of ABCA1 protein increased rapidly, and reached the peak at 8 h, then gradually declined. The ABCA1 protein levels were higher in amiloride group, ALLN group and amiloride＋ALLN group than that in control group. The differences of ABCA1 protein level were not statistically significant in amiloride group, ALLN group and amiloride＋ALLN group at 0,4 and 8 h. Whereas the ABCA1 protein level in amiloride＋ALLN group was higher than those in amiloride group and ALLN group at 12 and 16 h. Compared with the control group, calpain activities were decreased in amiloride group, ALLN group and amiloride＋ALLN group. There were no obvious differences in calpain activity among amiloride group, ALLN group and amiloride＋ALLN group at each time point. Conclusions Amiloride inhibits the degradation of ApoA1-induced ABCA1 and calpain activity in mice peritoneal macrophages in vivo. It indicates that NHE1 may be involved in ABCA1 degradation at least in part by changing the activity of calpain.

Abstract:Aim Macrophage apoptosis plays an important role in development of atherosclerotic plaques, necrotic lesions, plaque instability and acute vascular events, so the study of the regulation of Daxx macrophage apoptosis is favorable to reveal new drug targets, providing a theoretical basis for the occurrence of atherosclerosis. Methods The eukaryotic vector of Daxx and pCDNA3.1 were constructed to be stably transfected into RAW264.7 cells, the mRNA and protein expressions of Daxx were used by RT- PCR and Western blot respectively. The intracellular lipid droplets and lipid levels was assayed by enzyme fluorescent analysis. The growth inhibition and apoptotic effect of RAW264.7 cells induced by Chol∶MβCD were analyzed by MTT and flow cytometric analysis. The protein expressions of caspase3 was assayed by western blotting. Results RT-PCR and Western blot analysis showed that the expression of Daxx was significantly increased in gene-transfected RAW264.7 cells. Chol∶MβCD induced cholesterol accumulation and apoptosis in RAW264.7 cells was increased by Daxx. Caspase3 protein levels were significantly elevated in Daxx transfected cells. Conclusion Daxx overexpression could increase Chol∶MβCD induced apoptosis in macrophages.

Abstract:Aim To investigate the expression of endoplasmic reticulum stress(ESR) marker C/EBP homologous protein-10 (CHOP-10) in the human aortic endothelial cells (HAEC) under the ischemia and hypoxia stress and to study the effects of atorvastatin on the process. Methods The cultured HAEC were divided into normal control group, ischemia/hypoxia model group, ischemia/hypoxia plus CHOP-10 shRNA group and ischemia/hypoxia plus atorvastatin treatment group (0.1 mol/L, 1.0 mol/L, 10.0 mol/L). After 24 hours, the expression of CHOP-10 was detected by RT-PCR and the protein levels of CHOP-10, caspase-3 and caspase-8 were measured by Western blot. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) in the supernatant of cell culture medium were measured by ELISA. The CCK-8 test was used to measure cell proliferation. Results As compared with that of the control group, the CHOP-10 expression increased significantly in HAEC under the ischemia and hypoxia stress(P<0.01), the IL-6 and TNF-α level in the supernatant of cell culture medium were significantly higher than those of the control group(P<0.01). And the cells apoptosis increased and proliferation activity decreased significantly under the ischemia and hypoxia stress(P<0.01). The expression of CHOP-10 can be inhibited by atorvastatin in a dose-dependent manner in HAEC under the ischemia and hypoxia stress(P<0.01). Knock down CHOP-10 expression or application of atorvastatin treatment can inhibit cell apoptosis and increase proliferation activity in the cells of the ischemia/hypoxia group(P<0.01). Conclusions These findings indicate that ischemia and hypoxia can induce ESR and inflammation in HAEC. CHOP-10 expression up-regulated by ESR can increase cell apoptosis and decrease proliferation activity. Down-regulated CHOP-10 expression or application of atorvastatin treatment can reduce ESR under the ischemia and hypoxia stress and have a protective effect on vascular endothelial cells.

Abstract:Aim To investigate the relationship between the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and cyclooxygenase-2 (COX-2) expression in THP-1 monocytes. Methods Human THP-1 monocyte was used as the research cell, and the time-dependent expressions of STAT3 phosphorylation and COX-2 were detected after IL-6 treatment for 0 to 48 hours. THP-1 monocytes were pretreated with 100 μmol/L S3I-201(an specific inhibitor of STAT3 signaling) for 24 hours and then treated with 10 μg/L IL-6 for certain time. THP-1 monocytes were divided into 4 groups:control group, S3I-201 group, IL-6 group and IL-6＋S3I-201 group, then the changes of STAT3 phosphorylation and COX-2 expression were detected. COX-2 mRNA expression was detected by real-time fluorescence quantitative PCR. The levels of STAT3 phosphorylation and COX-2 protein expression were determinated by Western blot. Results IL-6 could obviously induce STAT3 phosphorylation and COX-2 expression via a time-dependent manner in THP-1 monocytes. Phosphorylation level of STAT3 increased after IL-6 stimulation for only 5 minutes (P＜0.001), meanwhile, COX-2 mRNA and protein expressions was significantly upregulated, reaching peak at 1 h and 2 h respectively (P＜0.001). Compared with control group, COX-2 mRNA and protein expressions were both markedly suppressed in S3I-201 group (P＜0.01). Compared with IL-6 group, phosphorylated STAT3 level was downregulated in IL-6＋S3I-201 group (P＜0.001), and COX-2 mRNA expression was also decreased (P＜0.001), with COX-2 protein expression clearly suppressed (P＜0.05). Conclusion IL-6 is capable of activating the STAT3 pathway in THP-1 monocytes, which may play a role in COX-2 expression and further affect the process of atherosclerotic disease.

Abstract:Aim To investigate the diagnostic value of dual-source CT prospective electrocardiographic gated low dose scan technology(DSCT) for patients with chest pain after percutaneous coronary intervention(PCI). Methods 84 patients with chest pain following PCI underwent DSCT from July 2014 to June 2015 in our hospital. Two independent experienced radiologists evaluated the image quality, and the images were target reconstructed on coronary arteries. All patients underwent coronary angiography(CAG) within 2 weeks after DSCT scan. CAG results were as the “gold standard”, and the specificity, sensitivity, negative predictive value and positive predictive value of DSCT were assessed for diagnosing coronary artery stenosis in patients with chest pain after PCI. Kappa test was used for comparison between DSCT and CAG in diagnosis consistency of coronary artery stenosis degree. Results The specificity, sensitivity, negative predictive value and positive predictive value of DSCT for diagnosing coronary artery stenosis were 85.5%, 96.6%, 94.6%, 90.4%. DSCT and CAG were highly consistent in the diagnosis of coronary artery stenosis degree(Kappa value＝0.858). The effective radiation dose of DSCT was 4.67±0.87 mSv. Conclusions DSCT coronary angiography is able to obtain high quality images in patients with chest pain after PCI. It is accurate to evaluate the degree of coronary artery stenosis, radiation dose is low, and it is worthy of clinical spread.

Abstract:Aim To analyze the correlation of autophagy level and carotid plaque of ischemic cerebrovascular disease, so as to provide data evidence to its pathomechanism. Methods 127 patients with ischemic cerebrovascular disease were divided into 3 groups according to carotid plague scores. The count and degree of cranial artery stenosis were observed with digital subtraction angiography. The fasting venous blood of patients was extracted to separate mononuclear cells and detect autophagosome by Dan acyl glutaric amine dyeing. At the same time, total protein of the fasting venous blood was extracted to detect autophagy related factor levels LC-Ⅱ/LC-Ⅰ and Beclin-1. Results There was difference in intima-media thickness, vascular stenosis number and degrees between different patches prioritization, and the Grade Ⅱ and Ⅲ were both higher than Grade Ⅰ, Grade Ⅲ was higher than Grade Ⅱ (P＜0.05). There were autophagy and autophagic apoptotic cells in the ultrathin section of peripheral blood mononuclear cells, and autophagy with green fluorescence was also observed in the leica microsystems after Dan acyl glutaric amine. There was difference in LC-Ⅱ/LC-Ⅰ and Beclin-1 levels between different patches prioritization, and the Grade Ⅱ and Ⅲ were both higher than Grade Ⅰ, Grade Ⅲ was higher than Grade Ⅱ (P＜0.05). We found that LC-3Ⅱ/LC-3Ⅰ and Beclin-1 protein expression level was positively correlated with intima-media thickness (R²=0.75, 0.79). Conclusion Autophagy can affect the carotid artery plaque of ischemic cerebrovascular disease, which may be the one of the important mechanisms.

Abstract:Aim To investigate the changes of blood lipid and cholesterol metabolism markers (cholesterol synthesis and absorption markers) in high-risk subjects of coronary heart disease before and after atorvastatin treatment, and to analyze the correlation between them. Methods 159 high-risk subjects of coronary heart disease were enrolled, and 20 mg atorvastatin per day was taken for four weeks. Blood lipids and cholesterol synthesis markers squalene/cholesterol (TC), desmosterol/TC, lathosterol/TC) and cholesterol absorption markers (sitosterol/TC, stigmasterol/TC, campesterol/TC) were determined respectively before and after treatment. According to the low density lipoprotein cholesterol (LDLC) level after atorvastatin treatment, the selected subjects were divided into two groups:good response group and poor response group. The changes of blood lipid and cholesterol metabolism markers and their correlation were analyzed in the two groups. Results After atorvastatin treatment, blood lipids were reduced in two groups, in addition to high density lipoprotein cholesterol increasing (9.4% in good response group, 7.4% in poor response group). TC, LDLC decreased significantly in good response group compared with the poor response group (P＜0.01). In good response group, the decrease of TC was positively correlated with the decrease of squalene/TC and sitosterol/TC (r＝0.247, r＝0.205, P＜0.05), and the decrease of LDLC was positively correlated with the decrease of campesterol/TC (r＝0.193, P＜0.05).In poor response group, the decrease of TC was negatively correlated with the decrease of stigmasterol/TC (r＝-0.388, P＜0.01), and the decrease of LDLC was negatively correlated with the decrease of squalene/TC, stigmasterol/TC and sitosterol/TC (r＝-0.280, P＜0.05; r＝-0.517, P＜0.01; r＝-0.320, P＜0.05). Conclusions After atorvastatin treatment, the changes of TC and LDLC in good response group are more obvious than those in poor response group, but the changes of cholesterol metabolism markers are not significant. In good response group, the decrease of TC and LDLC are positively correlated with cholesterol metabolism markers, whereas negative correlation is found in poor response group.

Abstract:Aim To study the effect of hypertension and diabetes on cardiac anatomic structure by Multilayer spiral CT. Methods 450 patients were categorized as essential hypertension group (n=150), essential hypertension with type 2 diabetes group (n=150) and control group (n=150), the cardiac structure according to the results of CT measurements was evaluated. Results For left ventricular cavity area and left ventricular maximum thickness, cross-sectional area of the heart between control group and essential hypertension groups, control group and hypertension and diabetes group, the differences was statistically significant (P＜0.05). For left ventricular minimum thickness between essential hypertension group and hypertension and diabetes group, the difference was statistically significant (P＜0.05). For coronal plane area and the volume of the heart between control group and hypertension and diabetes group, the difference was statistically significant (P＜0.05). Conclusion Hypertension can affect the cardiac structure mainly on the horizontal direction and diabetes can affect the cardiac structure on the horizontal and vertical direction.

Abstract:Aim To compare the expression of Toll like receptor 4(TLR4) in blood mononuclear cells and plasma high-sensitivity C-reactive protein (hs-CRP) between metabolic syndrome (MS) patients and simple hypertensive patients. Methods There were 62 EH patients and 45 patients with MS. The TLR4 positive rate in blood mononuclear cells was detected by flow cytometry. We also detected the plasma hs-CRP of the patiens. Single factor analysis was performed on TLR4, hs-CRP and other observation indexes (age, sex, total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), fasting blood glucose (FBG) and glycated hemoglobin (HbA1c)), and then multi-factor regression analysis was also performed. Results TLR4 and hs-CRP were statistically significant between MS group (5.7%±1.2% and 5.6±0.9 mg/L) and EH group (5.3%±0.9% and 5.0±0.8 mg/L) (t values were -3.274, -2.225, P values were 0.028, 0.01)； Single factor analysis showed that TLR4 was positively correlated with TC, LDL, HbA1c, FBG,2-hour postprandial blood glucose (2hPBG) and hs-CRP (P＜0.05), and hs-CRP was positively correlated with TC, LDL, HbA1c, FBG,2hPBG, TLR4 (P＜0.05)； Meanwhile, multi-factor regression analysis showed that hs-CRP and HbA1c were the most significant factors which affected TLR4(β values were 0.745,0.244, P values were 0.000,0.004), and TLR4 was the most significant factor which affected hs-CRP (β=0.943, P=0.000). Conclusion It is MS patients that have higher TLR4 positive rate in mononuclear cells and plasma hs-CRP compared with EH patients. TLR4 positive rate and plasma hs-CRP levels of MS patients are positively correlated. And TLR4 may be involved in the development and progression of MS.

Abstract:Aim To study the relationship between arterial stiffness and red blood cell parameters. Methods304 patients were chosen in the Medical Center of the Southern District of Guang'anmen Hospital of China Academy of Chinese Medical Sciences in July 2014. The medical history, measured height, weight, blood pressure, blood routine, biochemical indicators were asked, and Omron BP-203 RPE Ⅲ arterial stiffness detector was applied to test their arterial elasticity. According to brachial-ankle pulse wave velocity (baPWV), they were divided into normal group (n＝117 ), mild sclerosis group (n＝112) and atherosclerosis group (n＝75), and red blood cell parameters were compared among the three groups. Results The mean corpuscular volume (MCV) and red blood cell distribution width-correlation variance(RDW-CV) in the atherosclerosis group were significantly higher than that in the normal group (P<0.05 or P<0.01). The red blood cell distribution width-standard deviation (RDW-SD) in the atherosclerosis group was higher than that in the mild sclerosis group (P<0.05). The RDW-SD in the mild sclerosis group was higher than that in the normal group (P<0.05). Correlation analysis showed hemoglobin (HGB), hematocrit (HCT), MCV, mean corpuscular hemoglobin (MCH), RDW-CV, RDW-SD and baPWV were positively correlated. Multiple linear regression analysis showed the final regression equation included indicators was RDW-SD, HGB, the regression equation was baPWV＝-898.411＋39.657×RDW-SD＋3.171×HGB. Conclusion RDW-SD have a certain degree of clinical reference for the evaluation of atherosclerosis, while HGB is the impact factor of atherosclerosis.

Abstract:Aim To investigate the relationship between serum total bilirubin level and the major adverse cardiovascular events (MACE) in peri operation period undergoing percutaneous coronary intervention (PCI) in patients with unstable angina pectoris. Methods Analyse 1113 unstable angina pectoris patients underwent PCI from January 2012 to March 2015, statisticiy summarize the serum total bilirubin and other biochemical parameters, obtain the data of clinical characteristics and PCI, record the occurrence of MACE in peri operation period. Patients were divided into MACE group and non MACE group. Results Serum total bilirubin level in MACE group obviously decreased than that in the non MACE group, the difference was statistically significant (P＜0.05), the application of COX regression multivariate analysis showed that increase of serum total bilirubin was an independent protective factor of MACE in peri operation period undergoing PCI in unstable angina pectoris patients (RR＝0.7,5%CI was 0.867～0.970, P＜0.01). Conclusion High serum total bilirubin is an independent protective factor of MACE in peri operation period undergoing PCI in unstable angina pectoris patients.

Abstract:Aim To investigate the effect of exercise load test on QT dispersion in patients with coronary slow flow (CSF). Methods 81 cases of CSF patients with chest pain underwent coronary angiography, without coronary artery obvious stenosis (stenosis of the lumen diameter＜40%) were selected as the slow blood flow group. 80 cases with normal coronary angiography and exercise load test electrocardiogram negative were selected as the control group. Maximum corrected QT interval (QTc_max), minimum corrected QT interval (QTc_min) and corrected QT dispersion (QTcd) were calculated for each case before and after exercise. Results At rest time, QTc_max in the slow blood flow group was significantly longer than that in the control group (P＜0.05), the QTcd of the slow blood flow group increased significantly compared with the control group (P＜0.05), but there was no significant difference in QTc_min between the two groups. After exercise, the QTc_max and QTc_min in the slow blood flow group were significantly longer than those in the control group (P＜0.05), and QTcd significantly increased compared with the control group (P＜0.05). In the slow blood flow group, only 9 cases of exercise load test were positive, accounting for 11.11%. After exercise, the QTcd was significantly decreased compared with rest in the slow blood flow group (46.41±12.21 ms vs 62.81±17.18 ms, P＜0.05). In the control group, there was no significant change of QTcd before and after exercise. Conclusion QTcd in CSF patients is higher than that in normal person, and the exercise will make it significantly reduced.

Abstract:Aim To investigate the treatment efficacy of Tongxinluo compared with statins in patients with carotid atherosclerotic plaques. Methods We systematicly and exhaustively retrieved the Chinese and foreign language databases from their establishment date to May 1, 2015 to collect the randomized, controlled and clinical trials about the treatment efficacy of Tongxinluo compared with statins in patients with carotid atherosclerotic plaques, and then the RevMan 5.2 soft ware was used for Meta analysis. Results A total of 23 randomized controlled trials were included, involving 2355 patients with mean duration of 20±7 weeks. The results of Meta analysis showed the single use of Tongxinluo and statins in improving carotid artery intima-media thickness (IMT) and blood lipid levels had no significant difference (MD was -0.06, 95%CI was -0.17~0.05, P＝0.26 and MD was 0.19, 95%CI was -0.00~0.38, P＝0.05). But the single use of Tongxinluo had more advantages than statins in improving triglyceride (triglyceride,TG) level (MD was -0.28, 95%CI was -0.44~-0.11, P＝0.001). Tongxinluo combined with statins had more advantages than single using statins in the improvement of patients with IMT, plaque area, plaque score, blood lipid level and C-reactive protein (CRP) (P＜0.01). However, as to evaluate the adverse reactions, Tongxinluo had less percentage than statins (OR was 0.44, 95%CI was 0.27~0.73, P＝0.001). Conclusion In the treatment of patients with carotid atherosclerotic plaques, Tongxinluo combined with statins is the best therapeutic scheme in our study.

Abstract:Aim To assess the efficacy and safety of PCSK9 antibody AMG145 on lipid-lowering by a meta-analysis. Methods Such database as PubMed, Cochrane Library, EMBase, Web of Science, CNKI, CBM were searched from 2003 to Mar 13, 2015 for randomly collecting case-control clinical trial of AMG145 on lipid-lowering. Assessment and data extraction were conducted by two reviewers independently, meta-analysis was performed by RevMan5.3 software. Results 9 studies involving 2965 patients were included, including 5 Phase 2 and 4 Phase 3 clinical trials, all literatures were published by English. The results of meta-analysis showed that:compared with PBO AMG145 can significantly lower LDLC, Lp(a), ApoB/ApoA1 and elevate HDLC after 12 weeks medication(P＜0.01)； there were no significant differences of total adverse events, myodynia, nasopharyngitis, injection sites reaction, headache and ALT/AST≥3 times ULN between AMG145 and PBO(P＞0.05). Conclusion AMG145 can lower lipid effectively and safely.

Abstract:Tissue factor is closely related to the initiation and progression of atherosclerosis, and tissue factor pathway inhibitor(TFPI) is the main inhibitor of tissue factor-mediated coagulation. Ample experimental evidence indicates that TFPI has inhibitory effect on endothelial cell activity, the function of macrophages and smooth muscle cell proliferation and migration. This review focusses on the inhibitory effects of TFPI on the initiation and progression of atherosclerosis.

Abstract:Intraplaque angiogenesis induced by factors such as hypoxia and inflammation, plays a vital role in both occurrence and progression of atherosclerosis plaque. Not only the neovessels can undermine the stability of plaque by deteriorating inflammation and promoting intraplaque hemorrhage, which may lead to deadly acute coronary syndrome, the neovessels also can benefit the plaque by relieving oxygen, reducing cellular necrosis and providing a functional pathway to get deleterious substances out of the plaque. Although antiangiogenic therapy has been applied into clinical practice, treatment of plaques with angiogenesis are still well unanswered. This paper reviews the formation and progression of the angiogenesis in atherosclerosis, and summarizes the due effects of angiogenesis on the plaque stability and the current status of antiangiogenic therapy.

Abstract:Statins,3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, inhibit the rate-limiting enzyme in cholesterol synthesis and lead to a significant reduction of plasma lipid concentrations. As a clear correlation exists between serum cholesterol and cardiovascular risk, statins have become increasingly important in current preventive medicine. It is now widely accepted that cardiovascular disease prevention by statins is dependent not only on their lipid lowering effects, but also on their beneficial effects on anticoagulation etc. Anticoagulant effects of statins included prevention of venous thromboembolism, influence on the expression of coagulation factors, impact on physiological anticoagulants, suppression of inflammation and improvement in endothelial function. In this review, we provide an update on the current understanding of the interactions between statins and blood coagulation.

Abstract:Hyperlipidemia and osteoporosis are metabolic diseases. In clinic, patients with hyperlipidemia are often diagnosed with osteoporosis. Recent studies have shown that hyperlipidemia could induce bone metabolic disorders to exacerbate the progression of osteoporosis, suggesting that hyperlipidemia is strongly linked to the occurrence and development of osteoporosis. To date, the potential pathophysiological mechanisms of hyperlipidemia induce inflammation, oxidative stress, abnormal accumulation of lipid and lipid oxidation on bone metabolism are gradually clarified. This article reviewes the mechanisms of how hyperlipidemia initiates and promotes osteoporosis. With it, we desire to provide new approaches for the treatment of hyperlipidemia and osteoporosis.