贾彦俊
中国医学科学院阜外医院 保卫处
OBJECTIVE:To investigate the short- and long-term effects of Xuezhikang (XZK), an extract of cholestin, on proprotein convertase subtilisin/kexin type 9 (PCSK9) level.METHODS:Thirty rats were randomly divided into three groups and were given saline, XZK 1,200 mg/kg or lovastatin 10 mg/kg respectively by daily gavage for 3 days (n=10 for each). Sixteen patients without previous lipid-lowering drug treatment for dyslipidemia received XZK 1,200 mg daily for 8 weeks. Fasting blood samples and liver tissue were collected at day 3 for rats, while the blood samples were obtained at baseline and week 8 from patients. The serum PCSK9 and lipid profile were measured. The expression of hepatic low density lipoprotein (LDL) receptor and sterol regulatory element binding protein 2 (SREBP-2) were measured by real time-PCR.RESULTS:PCSK9 levels in rats were significantly increased in the XZK and lovastatin groups (P=0.002, P=0.003 vs. control) at day 3, while no significant differences were found in the levels of lipid parameters. PCSK9 levels in patients increased by 34% (P=0.006 vs. baseline) accompanied by total cholesterol and LDL-cholesterol decreased by 22% and 28% P=0.001, P=0.002 vs. baseline). The hepatic mRNA levels of LDL-receptor and SREBP-2 were significantly increased in the XZK and lovastatin groups.CONCLUSION:XZK has significant impact on PCSK9 in a short- and long-term manner in both rats and humans. Moreover, the data indicated that as lovastatin, XZK increased PCSK9 levels through SREBP-2 pathway.
Chinese journal of integrative medicine 2016
BACKGROUND:Previous studies including our group have indicated the effects of ezetimibe on increased plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration, while the rapid expression in different organs and the potential molecular mechanisms for this impact have not been carefully evaluated.METHODS:Thirty rats were randomly divided into two groups (n = 15 for each), which were orally administrated with ezetimibe (10 mg/kg/day) or normal saline. Blood samples were obtained at day 3 after orally administration, and the PCSK9 levels were determined by ELISA. We further analyzed the mRNA expression of PCSK9, low-density lipoprotein receptor (LDLR), sterol regulator element-binding protein 2 (SREBP2), and hepatocyte nuclear factor 1 alpha (HNF-1α) by real-time PCR, as well as the protein expression by western blot, in liver, intestine and kidney respectively.RESULTS:Ezetimibe significantly increased plasma PCSK9 levels compared with control group, while there was no significant difference between the two groups with regard to lipid profile at day 3. Moreover, ezetimibe remarkably increased the expression of PCSK9, LDLR, SREBP2 and HNF-1α in liver. Enhanced expression of PCSK9, LDLR and SREBP2 protein were found in intestine and kidney, while no changes in the expression of HNF-1α were observed in intestine and kidney of rats with ezetimibe treatment.CONCLUSIONS:The data demonstrated that ezetimibe increased PCSK9 expression through the SREBP2 and HNF-1α pathways in different organs, subsequently resulting in elevated plasma PCSK9 levels prior to the alterations of lipid profile in rats.
Journal of translational medicine 2015
UNLABELLED:Backround N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor in acute coronary artery disease (CAD). Little is known about patients with stable CAD, especially Chinese patients with CAD. The aim of the present study was to investigate the association of NT-proBNP levels with the severity of CAD in patients with normal left ventricular ejection fraction.METHODS:A total of 658 consecutive patients were divided into two groups based on angiograms: CAD group (n = 484) and angiographic normal control group (n = 174). The severity of CAD was evaluated by modified Gensini score, and its relationship with NT-proBNP was analyzed.RESULTS:The prevalence of risk factors such as age, male gender, diabetes mellitus (DM), dyslipidemia, smoking, and family history of CAD in the CAD group were higher than that in the control group. In multivariate regression model analysis, age, gender, and DM were determinants of the presence of CAD. NT-pro BNP was found to be an independent predictor for CAD (OR:1.66 (95% CI: 1.06-2.61), P < 0.05). In a receiver operating characteristic (ROC) curve analysis, an NT-proBNP value of 641.15 pmol/L was identified as a cut-off value in the diagnosis or exclusion of CAD (area under curve (AUC) = 0.56, 95% CI: 0.51-0.61). Furthermore, NT-proBNP was positively correlated with Gensini score (r = 0.14, P < 0.001) in patients with CAD.CONCLUSION:NT-proBNP was an independent predictor for Chinese patients with CAD, suggesting that the NT-proBNP level might be associated with the presence and the severity of CAD.
Chinese medical journal 2014
BACKGROUND:Several studies investigating the prognostic utility of interleukin-10 (IL-10) in patients with acute coronary syndrome (ACS) have provided conflicting findings. The aim of the study was to assess the existing evidence regarding association between serum IL-10 levels and adverse events.METHODS:Literature search was performed in PubMed, EMBASE, and Cochrane Trials Register databases from their inception to September 30, 2012. In addition, reference lists of the included articles and their related citations in PubMed were also reviewed for additional pertinent studies.RESULTS:A total of 12 eligible studies comprising a total of 5882 patients were identified. The pooled relative risks for both studies reporting the risk estimates by IL-10 categories and studies reporting the risk estimates by unit IL-10 indicated an association between high IL-10 levels and adverse events. Sensitivity and subgroup analysis indicated that the results obtained in IL-10 categories were not stable.CONCLUSIONS:Data from our meta-analysis supported the existence of a relationship between high serum IL-10 levels and adverse events in patients with ACS. Large study with longer follow-up is needed to confirm the findings.
Chinese medical journal 2014
BACKGROUND:Obesity is associated with unfavorable alternations in plasma lipid profile and a broad spectrum of cardio-metabolic disorders. Proprotein convestase subtilisin kexin type 9 (PCSK9) is a novel circulating protein that promotes hypercholesterolemia by decreasing hepatic low lipoprotein density receptor (LDLR) protein. However, the relationship between PCSK9 concentration and lipid profile in an obesity condition has less been investigated.OBJECTIVE:To examine the changes of plasma PCSK9 concentration in a rat model fed with high fat diet (HFD) and its correlation to lipid profile, body weight and ageing.METHODS:Twenty male Sprague Dawley (SD) rats were divided into two groups, control group (fed with normal pellet for 4 weeks), and high-fat diet group (fed with 3% cholesterol enrich diet for 4 weeks). Blood samples of rats were obtained before and at days 14, 21, and 28 in both groups. The body weight, plasma metabolic parameters (glucose, lipid profile) and PCSK9 were determined at indicated time points.RESULTS:The body weights were significantly increased in rats fed with HFD compared to that in rats with normal pellets at day 28. Additionally, total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels in rat fed with HFD were also higher than that in rats fed with control diet while decreased high density lipoprotein cholesterol (HDL-C) levels were found in rats with HFD at day 28. More interesting, there were no differences of plasma PCSK9 concentrations as well as hepatic expression of LDLR between the two groups at day 28.CONCLUSIONS:Although the body weight and LDL-C were significantly increased in rats fed with HFD at 4 weeks, there were no differences of changes in plasma PCSK9 concentration and LDLR expression of liver tissue in both groups at baseline and day 28, suggesting that dyslipidemia in the rat model with HFD appears not to be associated with PCSK9-LDLR pathway but ageing.
Journal of geriatric cardiology : JGC 2013
