Hyperlipidemias: Liu J

Kong WJ, Liu J, Jiang JD. · Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China. · J Mol Med. · Pubmed #16292665 No free full text.

Abstract: The low-density lipoprotein (LDL) receptor is a transmembrane glycoprotein that mediates the binding and endocytosis of lipoproteins containing apolipoprotein B and E, especially the cholesterol-rich LDL. Mutations in the LDL receptor gene can produce dysfunctional LDL receptors and cause familial hypercholesterolemia. The expression of the LDL receptor gene is under an intriguing regulation by sterol and nonsterol mediators either at the transcriptional level or at the posttranscriptional level, both of which are linked to cell signaling pathways. Upregulation of liver LDL receptor expression is effective in treating hypercholesterolemia. In this review, we focus on the latest progress on the mechanisms and regulation of the LDL receptor gene expression.

Wang A, Yu BN, Luo CH, Tan ZR, Zhou G, Wang LS, Zhang W, Li Z, Liu J, Zhou HH. · Department of Health Toxicology, School of Public Health, Pharmacogenetics Research Institute, Central South University, Changsha, Hunan, 410078, China. · Eur J Clin Pharmacol. · Pubmed #15650881 No free full text.

Abstract: OBJECTIVES: To determine the frequencies of CYP3A4 alleles (CYP3A4*4,*5 and *6) in Chinese hyperlipidemic patients and to observe the impact of CYP3A4*4 (Ile118Val) genetic polymorphism on the lipid-lowering effects of simvastatin and on the activity of CYP3A4. METHODS: From hospitalized and non-hospitalized patients, 211 unrelated hyperlipidemic patients were recruited for genotyping. CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis. Of the non-hospitalized hyperlipidemic patients, 8 with CYP3A4*1/*1 and 8 with CYP3A4*1/*4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks. Serum triglycerides (TG), cholesterol (CHO) and low-density lipoprotein (LDL) levels were determined using an automated analyzer (Hitachi 747, Boehringer Mannheim, Mannheim, Germany). CYP3A4 activity was determined by the ratio of 6-hydroxycortisol to free cortisol (6-OHC/FC) in the morning spot urine with a high-throughput liquid chromatography-tandem mass spectrometry method. RESULTS: Of 211 subjects, 14 (allele frequency 3.32%) were heterozygous for CYP3A4*4 (Ile118Val). Nevertheless, no subjects with a CYP3A4*5 or CYP3A4*6 allele or homozygous for CYP3A4*4 were identified. The ratio of 6beta-OHC/FC was 9.9 +/- 13.7 and 56.6 +/- 35.7 in subjects with the Ile118Val variant (n = 8) and in CYP3A4 wild-type subjects (n = 8), respectively (P = 0.0039). After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1 +/- 7.6% versus 25.1 +/- 8.3% (P = 0.034) and of 35.8 +/- 9.6% versus 22.0 +/-20.4% (P = 0.0015) (means +/- SD), respectively. We found no statistically significant difference in the reductions of LDL between subjects carrying the *1 and *4 genotypes (29.0 +/- 7.4% versus 36.8 +/- 8.8%, P = 0.0721). CONCLUSIONS: The allele frequency of CYP3A4*4 was 3.32% among the hyperlipidemic patients from the Chinese mainland. CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin.

Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. · Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, 100050, China. · Nat Med. · Pubmed #15531889 No free full text.

Abstract: We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.

Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB, Anonymous00313. · Lipid Research Clinic, Washington University, St Louis, MO 63110-1093, USA. · Mayo Clin Proc. · Pubmed #15132403 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy and safety of 10 mg of ezetimibe coadministered with simvastatin with the safety and efficacy of simvastatin monotherapy for patients with hypercholesterolemia. PATIENTS AND METHODS: This multicenter double-blind, placebo-controlled, factorial study enrolled 887 patients with hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C], 145-250 mg/dL; triglycerides, < or = 350 mg/dL). Patients were randomized to 1 of 10 treatments--placebo, ezetimibe at 10 mg/d, simvastatin at 10, 20, 40, or 80 mg/d, or simvastatin at 10, 20, 40, or 80 mg/d plus ezetimibe at 10 mg/d for 12 weeks. The study began March 13, 2001, and ended January 8, 2002. The primary efficacy end point was the mean percent change in LDL-C levels from baseline to study end point (last available postbaseline LDL-C measurement) for the pooled ezetimibe/simvastatin group vs the pooled simvastatin monotherapy group. RESULTS: Coadministration of ezetimibe/simvastatin was significantly (P<.001) more effective than simvastatin alone in reducing LDL-C levels for the pooled ezetimibe/simvastatin vs pooled simvastatin analysis and at each specific dose comparison. The decrease in LDL-C levels with coadministration of ezetimibe and the lowest dose of simvastatin, 10 mg, was similar to the decrease with the maximum dose of simvastatin, 80 mg. A significantly (P<.001) greater proportion of patients in the ezetimibe/simvastatin group achieved target LDL-C levels compared with those in the monotherapy group. Treatment with ezetimibe/simvastatin also led to greater reductions in total cholesterol, triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels compared with simvastatin alone; both treatments increased high-density lipoprotein cholesterol levels similarly. The safety and tolerability profiles for the ezetimibe/simvastatin and monotherapy groups were similar. CONCLUSION: Through dual inhibition of cholesterol absorption and synthesis, coadministration of ezetimibe/simvastatin offers a highly efficacious and well-tolerated lipid-lowering strategy for treating patients with primary hypercholesterolemia.

Cheng J, Zhao D, Zeng Z, Critchley JA, Liu J, Wang W, Sun J, Capewell S. · Department of Epidemiology, Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing Anzhen Hospital affiliated to the Capital Medical University, Beijing, PR China. · BMC Public Health. · Pubmed #19159492 links to  free full text

Abstract: BACKGROUND: Recent, dramatic increases in coronary heart disease (CHD) mortality in China can be mostly explained by adverse changes in major cardiovascular risk factors. Our study aimed to assess the potential impact of subsequent changes in risk factors and population ageing on CHD deaths in Beijing between 1999 and 2010. METHODS: The previously validated IMPACT model was used to estimate the CHD deaths expected in 2010, with treatment uptakes being held constant at levels measured in 1999, comparing three scenarios: a) taking into account the ageing of the population but assuming no further changes in major risk factor levels from 1999 or, b) if recent risk factor trends continued until 2010 or, c) if there was a 0.5% annual reduction in each risk factor. RESULTS: Population ageing alone would result in approximately 1990 additional deaths in 2010 compared with 1999, representing an increase of 27%. Continuation of current risk factor trends would result in approximately 3,015 extra deaths in 2010, [a 40% increase]; three quarters of this increase would be attributable to rises in total cholesterol levels. Thus, demographic changes and worsening risk factors would together result in a 67% increase in CHD deaths. Conversely, assumed 0.5% annual reductions in risk factors (a mean population level decline of 0.3 mmol/L for total cholesterol in both genders, and smoking prevalence declining by 3.0% for men and 4.1% for women, body mass index by 1.3 kg/m2 for men and 1.4 kg/m2 for women, diabetes prevalence by 0.4% in both genders, and diastolic blood pressure by 4.7 mmHg for men and 4.4 mmHg for women) would result in some 3,730 fewer deaths, representing a 23% decrease overall. These findings remained consistent in sensitivity analyses. CONCLUSION: CHD death rates are continuing to rise in Beijing. This reflects worsening risk factor levels, compounded by demographic trends. However, the adverse impact of population ageing on CHD burden could be completely offset by eminently feasible improvements in diet and smoking.

Zhang J, Liu J, Li L, Xia W. · State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China. · Nutr Res. · Pubmed #19083436 No free full text.

Abstract: The hypolipidemic mechanism of chitosan was investigated in male Sprague-Dawley rats. Animals were divided into 5 groups (n = 8): a normal fat control group, a high-fat control group (HF), a positive control group (CR), and 2 chitosan groups (CIS1 and CIS2). Chitosan was fed at the beginning (CIS1) and after 2 weeks (CIS2). A commercial diet with 5% (wt/wt) cellulose (HF), cholestyramine (CR), or chitosan (CIS1, CIS2) was fed for 6 weeks. Chitosan did not affect food intake but decreased body weight gain and significantly increased fecal fat and cholesterol excretion, reduced the lipid level in plasma and liver, increased liver hepatic and lipoprotein lipase activities compared with HF (P < .05), and tended to relieve the degenerated fatty liver tissue. No significant differences in all measurements were found between the CIS1 and CIS2 groups although the CIS1 rats exhibited lower lipid levels compared to those in the CIS2 group. The results suggest that chitosan reduced the absorption of dietary fat and cholesterol in vivo and could effectively improve hypercholesterolemia in rats.

Bays H, Sapre A, Taggart W, Liu J, Capece R, Tershakovec A. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. · Curr Med Res Opin. · Pubmed #18782465 No free full text.

Abstract: OBJECTIVE: This study evaluated the long-term safety and tolerability of ezetimibe/simvastatin coadministration therapy compared to simvastatin monotherapy in patients with primary hypercholesterolemia. RESEARCH DESIGN AND METHODS: After completing a 12-week randomized, double-blind, placebo-controlled, factorial, 10-armed study comparing ezetimibe 10 mg/simvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg; or placebo, 768 patients entered a 48-week extension, with randomized, blinded, reassignment of the simvastatin 10 mg, ezetimibe, and placebo groups to one of the ezetimibe/simvastatin groups. Patients previously receiving ezetimibe/simvastatin combination therapy, or simvastatin 20, 40, and 80 mg monotherapy continued the same therapies in this 7-arm extension study. During the extension study, investigators assessed adverse events (AEs). MAIN OUTCOME MEASURES AND RESULTS: Ezetimibe/simvastatin (n = 539) and simvastatin monotherapy (n = 229) groups generally had a similar incidence of all clinical AEs (73 vs. 69%), treatment-related AEs (14 vs. 11%), clinical serious AEs (SAE) (5.2 vs. 2.6%), treatment-related SAEs (0.2 vs. 0%), discontinuations due to all clinical AEs (4.5 vs. 2.6%) and discontinuations due to treatment-related AEs (2.8 vs. 2.2%), respectively. The incidence of total laboratory-related AEs for the ezetimibe/simvastatin and simvastatin monotherapy groups was also similar (12.2 vs. 11.9%), as was treatment-related laboratory AEs (6.2 vs. 5.3%), laboratory SAEs (0 vs. 0%), treatment-related laboratory SAEs (0 vs. 0%), discontinuations due to laboratory AEs (3.0 vs. 0.9%) and discontinuations due to treatment-related laboratory AEs (3.0 vs. 0.4%), respectively. There were no cases of myopathy, rhabdomyolysis, or serious hepatotoxicity observed in any group during this extension study. CONCLUSIONS: During this 48-week extension study, the coadministration of ezetimibe/simvastatin was generally as well tolerated as simvastatin monotherapy. The direct application of study observations to clinical practice is limited by patient selection criteria and dosage regime, which randomly applied relatively high doses rather than titration which often occurs in clinical practice.

Takata Y, Liu J, Yin F, Collins AR, Lyon CJ, Lee CH, Atkins AR, Downes M, Barish GD, Evans RM, Hsueh WA, Tangirala RK. · Division of Endocrinology, Diabetes, and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-7073, USA. · Proc Natl Acad Sci U S A. · Pubmed #18337495 links to  free full text

Abstract: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPARdelta) has been shown to improve insulin resistance, adiposity, and plasma HDL levels. However, its antiatherogenic role remains controversial. Here we report atheroprotective effects of PPARdelta activation in a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by increased vascular inflammation related to repression of an antiinflammatory corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the PPARdelta agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII-accelerated atherosclerosis without altering blood pressure and increased vascular expression of Bcl-6, RGS4, and RGS5, which was associated with suppression of inflammatory and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated macrophages: PPARdelta activation increased both total and free Bcl-6 levels and inhibited AngII activation of MAP kinases, p38, and ERK1/2. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of PPARdelta activation to inhibit AngII signaling, which is atheroprotective.

Sun B, Xu DS, Jiang HC, Tai S, Cui YF, Xu J, Liu C, Meng QH, Liu J, Wu LF. · Department of Hepatobiliary and Pancreatic Surgery, First Clinical Hospital of Harbin Medical University, Harbin 150001, China. · Zhonghua Wai Ke Za Zhi. · Pubmed #17825192 No free full text.

Abstract: OBJECTIVE: To investigate the principle and measures of combined treatment of the patients with hyperlipidemic severe acute pancreatitis (HL-SAP). METHODS: The clinical data of 54 patients with HL-SAP including two phases from January 1996 to December 2000 and from January 2001 to August 2006 were analyzed retrospectively. In the first phase, 25 patients were performed by routine methods to decrease triglyceride, or additional operative treatments. In the second phase, 29 cases were treated by multiple ways of non-operative combined therapy, or additional operative treatments mainly by minimally invasive procedures. RESULTS: Among 54 cases with HL-SAP, 33 cases (61.1%) received non-operative therapy and 21 cases (38.9%) received surgical intervention. Overall mortality was 18.5% (10/54). In the first phase of 25 cases, the mortality in non-operative group and surgical intervention group was 21.4% (3/14) and 36.3% (4/11), respectively. In the second phase of 29 cases, the mortality in non-operative group and surgical intervention group was 10.5% (2/19) and 10.0% (1/10), respectively. The overall curative rate, morbidity, overall mortality, content of triglyceride at the fourth day after onset, APACHE II score at the fourth day after onset and average stay were obviously improved in the second phase compared with the first phase (P < 0.05). CONCLUSIONS: According to individualized therapy principles, treatment for HL-SAP should emphasis on multiple ways of non-operative combined therapy and appropriate choices of the timing, indication in surgical intervention. And the choice of operative procedure should follow the principle of minimally invasive surgery. Meanwhile, pay more attention to monitoring and controlling the level of triglyceride post-discharge for the patients with the history of HL-SAP.

Zhou Y, Abidi P, Kim A, Chen W, Huang TT, Kraemer FB, Liu J. · VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #17761945 links to  free full text

Abstract: OBJECTIVE: In our previous studies that examined in vivo activities of oncostatin M (OM) in upregulation of hepatic LDL receptor (LDLR) expression, we observed reductions of LDL-cholesterol and triglyceride (TG) levels in OM-treated hyperlipidemic hamsters. Interestingly, the OM effect of lowering plasma TG was more pronounced than LDL-cholesterol reduction, suggesting additional LDLR-independent actions. Here, we investigated mechanisms underlying the direct TG-lowering effect of OM. METHODS AND RESULTS: We demonstrate that OM activates transcription of long-chain acyl-coenzymeA (CoA) synthetase isoforms 3 and 5 (ACSL3, ACSL5) in HepG2 cells through the extracellular signal-regulated kinase (ERK) signaling pathway. Increased acyl-CoA synthetase activities in OM-stimulated HepG2 cells and in livers of OM-treated hamsters are associated with decreased TG accumulation and increased fatty acid beta-oxidation. We further show that overexpression of ACSL3 or ACSL5 alone in the absence of OM led to fatty acid partitioning into beta-oxidation. Importantly, we demonstrate that transfection of siRNAs targeted to ACSL3 and ACSL5 abrogated the enhancing effect of OM on fatty acid oxidation in HepG2 cells. CONCLUSIONS: These new findings identify ACSL3 and ACSL5 as OM-regulated genes that function in fatty acid metabolism and suggest a novel cellular mechanism by which OM directly lowers the plasma TG in hyperlipidemic animals through stimulating the transcription of ACSL specific isoforms in the liver.

Zhao D, Grundy SM, Wang W, Liu J, Zeng Z, Wang W, Wu Z. · Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. · Am J Cardiol. · Pubmed #17719329 No free full text.

Abstract: This study aimed to examine the relation between central obesity and other metabolic disorders of metabolic syndrome (MS) and compare the long-term risks of cardiovascular disease (CVD) between patients with MS with or without central obesity in middle-aged Chinese. The study included 30,378 Chinese aged 35 to 64 years at baseline with complete measurements for MS components and follow-up data for new acute CVD events from 1992 to 2003. The 10-year relative and absolute CVD risks in the MS groups with or without central obesity were compared. Results showed that 78% of patients with MS had central obesity and 22% with MS had no central obesity, diagnosed using updated Adult Treatment Panel III criteria with cut-off values appropriate for Asian populations. Central obesity, as well as other metabolic disorders in patients with MS, except for increased triglycerides, increased CVD risk significantly. There were no significant differences in 10-year absolute and relative risks of coronary heart disease events and ischemic CVD events between the 2 MS groups. In conclusion, MS with or without central obesity has a significantly increased 10-year risk of CVD in middle-aged Chinese.

Chang XT, Wang ZH, Du X, Dong MG, Hou LJ, Liu J, Wang J, Zhou JG. · Department of Biochemistry, Hebei North University, Zhangjiakou 075029, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #16733910 No free full text.

Abstract: OBJECTIVE: To explore the effect of polymorphism in codon Ala54Thr of human intestinal fatty acid-binding protein gene (IFABP) on the therapeutic efficacy of fenofibrate. METHODS: Totally 147 patients with hyperlipidemia [72 men mean age: (56.2 +/- 8.63) years; 75 women mean age: (58.4 +/- 9.12) years] were enrolled. IFABP genotypes were detected by polymerase chain reaction, Hha I digestion, and sequencing. Four weeks before and after treatment, the levels of fasting serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein A I (apoA I) and apolipoprotein B (apoB) were detected with biochemical techniques. RESULTS: The frequency of IFABP genotype was 0.47 for A/A, 0.37 for A/T, and 0.16 for T/T, and the allelic frequency was 0.65 for A and 0.35 for T. No significant different was found in lipid levels in every genotype before treatment (P > 0.05). After 4 weeks of treatment, the levels of TC, TG, LDL-C, and apoB significantly decreased (P < 00.01), and the levels of HDH-C and apoA I significantly increased (P < 0.01). The total therapeutic efficacy on A54A and A54T were 97% and 95%, respectively. In the patients with T54T genotype after treatment, no significant difference in lipids levels was found except TG (P < 0.05), and the total efficacy was only 38%. The total therapeutic efficacies of fenofibrate on A54A and A54T were higher than those of T54T, and there was significant different between A54A and T54T (P < 0.01). CONCLUSION: The polymorphism of human IFABP gene in hyperlipidemia is related with the therapeutic efficacy of fenofibrate, and the T54T IFABP genotype may have strong negative effect on such efficacy.

Zhao LJ, Zhao D, Liu J, Wang W, Wu GX, Qin LP, Liu J, Liu S, Wang WH, Zeng ZC. · Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Capital University Affiliationg Beijing Anzhen Hospital, Beijing 100029, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #16202255 No free full text.

Abstract: OBJECTIVE: To Study the association between the level of serum uric acid and triglyceride in a Chinese population. METHODS: In 1999, a cross-sectional study was carried out in a natural population of Beijing, using stratified-random sampling method. Serum uric acid and triglyceride were measured in 1239 subjects. RESULTS: The prevalence of hypertriglyceridemia significantly increased with increased level of serum uric acid among both the men and women. After adjusting BMI, HOMA index and alcohol consumption level with stratified methods, the incidence of hypertriglyceridemia increased with increasing level of basal serum uric acid in different levels of BMI, HOMA index and alcohol consumption. After adjusting gender, age, BMI, HOMA index, total cholesterol, smoking and alcohol consumption, the results of multivariate logistic regression analyses indicated that the odds ratio for hypertriglyceridemia as compared with the lowest quartile of serum uric acid was 1.26 (P = 0.28) for the second quartile, 1.88 (P = 0.002) for the third quartile, and 3.36 (P < 0.001) for the highest quartile. CONCLUSIONS: Serum uric acid level was strongly associated with triglyceride independent of age, genders, smoking, alcohol consumption, obesity and insulin resistance.

Zhao LJ, Zhao D, Liu J, Wang W, Wu GX, Qin LP, Liu J, Liu S, Wang WH, Zeng ZC. · Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Capital University Affiliationg Beijing Anzhen Hospital, Beijing 100029, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #16202255 No free full text.

Abstract: OBJECTIVE: To Study the association between the level of serum uric acid and triglyceride in a Chinese population. METHODS: In 1999, a cross-sectional study was carried out in a natural population of Beijing, using stratified-random sampling method. Serum uric acid and triglyceride were measured in 1239 subjects. RESULTS: The prevalence of hypertriglyceridemia significantly increased with increased level of serum uric acid among both the men and women. After adjusting BMI, HOMA index and alcohol consumption level with stratified methods, the incidence of hypertriglyceridemia increased with increasing level of basal serum uric acid in different levels of BMI, HOMA index and alcohol consumption. After adjusting gender, age, BMI, HOMA index, total cholesterol, smoking and alcohol consumption, the results of multivariate logistic regression analyses indicated that the odds ratio for hypertriglyceridemia as compared with the lowest quartile of serum uric acid was 1.26 (P = 0.28) for the second quartile, 1.88 (P = 0.002) for the third quartile, and 3.36 (P < 0.001) for the highest quartile. CONCLUSIONS: Serum uric acid level was strongly associated with triglyceride independent of age, genders, smoking, alcohol consumption, obesity and insulin resistance.

Abidi P, Zhou Y, Jiang JD, Liu J. · VA Palo Alto Health Care System, Palo Alto, CA 94304, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #16100034 links to  free full text

Abstract: OBJECTIVE: Our recent studies identified berberine (BBR) as a novel cholesterol-lowering drug that upregulates low-density lipoprotein (LDL) receptor expression through mRNA stabilization. Here, we investigated mechanisms underlying regulatory effects of BBR on LDL receptor (LDLR) messenger. METHODS AND RESULTS: We show that the extracellular signal-regulated kinase (ERK) signaling pathway is used primarily by BBR to attenuate the decay of LDLR mRNA in HepG2 cells. Using different reporter constructs, we demonstrate that BBR affects LDLR mRNA stability entirely through 3' untranslated region (UTR) in an ERK-dependent manner, and this stabilizing effect is more prominent in liver-derived cells than nonhepatic cell lines. In contrast to BBR, the mRNA stabilizing effect of bile acid chenodeoxycholic acid is mediated through the LDLR coding sequence, whereas the 5'UTR, 3'UTR, and the coding sequence of LDLR mRNA are all implicated in the action of phorbol 12-myristate 13-acetate. By performing UV cross-linking and SDS-PAGE, we identify 2 cytoplasmic proteins of 52 and 42 kDa that specifically bind to the LDLR 3'UTR in BBR-inducible and ERK-dependent manners. CONCLUSIONS: These new findings demonstrate that the BBR-induced stabilization of LDLR mRNA is mediated by the ERK signaling pathway through interactions of cis-regulatory sequences of 3'UTR and mRNA binding proteins that are downstream effectors of this signaling cascade.

Liu J, Zhao D, Liu J, Liu S, Qin LP, Wu ZS. · Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #16029634 No free full text.

Abstract: OBJECTIVE: To study the effect of lipoprotein lipase (LPL)-HindIII and PvuII polymorphisms on preheparin plasma LPL concentration and triglyceride. METHODS: A cross-sectional study was carried out in a general population of Beijing in 1999, using stratified-random sampling method. LPL-HindIII and PvuII polymorphism and preheparin plasma LPL concentration were determined in 670 individuals aged 45 - 64. RESULTS: (1) The frequencies of H1H1, H1H2, and H2H2 genotypes were 0.646, 0.322, and 0.031 respectively; and the frequencies of P1P1, P1P2, and P2P2 genotypes were 0.410, 0.472, and 0.118 respectively. The distribution of genotypes and that of alleles were homogeneous in both sexes. (2) The plasma LPL concentrations of the 12 type heterozygotes (H1H2 and P1P2) and those of the 22 type (H2H2 and P2P2) homozygotes were all higher than that of the 11 type homozygotes (H1H1 and P1P1) (all P < 0.01). And the LPL concentration varied greatly among different individuals of the same genotype. (3) Smoking, alcohol consumption, BMI, and waist level influenced LPL concentration more significantly in the H1H1 and P1P1 homozygotes and P1P2 heterozygotes. Multivariate analysis showed that smoking and obesity were independent influencing factors of serum LPL concentration (both P < 0.01). (4) The prevalence rate of hypertriglyceridemia was significantly different among different genotypes, the 11 type homozygotes having the highest rate, and the 22 type homozygotes having the lowest. In the same genotype, along with the increase of the serum LPL concentration the prevalence of hypertriglyceridemia decreased (P < 0.05). CONCLUSION: LPL-HindIII and PvuII polymorphisms are determinants of plasma LPL concentration. This genetic effect can be modified by some environmental factors, such as smoking and obesity.

Liu J, Zhao D, Liu J, Liu S, Qin LP, Wu ZS. · Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #16029634 No free full text.

Abstract: OBJECTIVE: To study the effect of lipoprotein lipase (LPL)-HindIII and PvuII polymorphisms on preheparin plasma LPL concentration and triglyceride. METHODS: A cross-sectional study was carried out in a general population of Beijing in 1999, using stratified-random sampling method. LPL-HindIII and PvuII polymorphism and preheparin plasma LPL concentration were determined in 670 individuals aged 45 - 64. RESULTS: (1) The frequencies of H1H1, H1H2, and H2H2 genotypes were 0.646, 0.322, and 0.031 respectively; and the frequencies of P1P1, P1P2, and P2P2 genotypes were 0.410, 0.472, and 0.118 respectively. The distribution of genotypes and that of alleles were homogeneous in both sexes. (2) The plasma LPL concentrations of the 12 type heterozygotes (H1H2 and P1P2) and those of the 22 type (H2H2 and P2P2) homozygotes were all higher than that of the 11 type homozygotes (H1H1 and P1P1) (all P < 0.01). And the LPL concentration varied greatly among different individuals of the same genotype. (3) Smoking, alcohol consumption, BMI, and waist level influenced LPL concentration more significantly in the H1H1 and P1P1 homozygotes and P1P2 heterozygotes. Multivariate analysis showed that smoking and obesity were independent influencing factors of serum LPL concentration (both P < 0.01). (4) The prevalence rate of hypertriglyceridemia was significantly different among different genotypes, the 11 type homozygotes having the highest rate, and the 22 type homozygotes having the lowest. In the same genotype, along with the increase of the serum LPL concentration the prevalence of hypertriglyceridemia decreased (P < 0.05). CONCLUSION: LPL-HindIII and PvuII polymorphisms are determinants of plasma LPL concentration. This genetic effect can be modified by some environmental factors, such as smoking and obesity.

Cheng Z, Lü J, Liu J. · Pharmacy College of Jinan University, Guangzhou. · Zhong Yao Cai. · Pubmed #15807245 No free full text.

Abstract: OBJECTIVE: To observe the effects of Peristrophe roxburghiana (HSX) on the blood pressure in renal hypertensive and hyperlipidemic rats (RHHR), and investigate the possible mechanisms of its pharmacological effects. METHODS: The two-kidney, two-clip method was used to produce the renovascular hypertensive rats, then high lipid emulsion was administered to produce the model of hyperlipidemic rats. Drugs were administered for 5 weeks. Blood pressure was measured weekly before and after administration. After rats were killed at the end of the 5th week,blood was sampled to measure plasma angiotensin IT and serum NO. Angiotensin II in the thoratic aorta was measured too. RESULTS: The BP decreased significantly to the end of 5th week (P < 0.05) after treatment of 1-2 weeks with HSX. HSX (H or L dosage) increased the level of serum NO evidently at the end of the experiment. No significant statistical difference was found in the level of plasma angiotensin, but HSX(H) and captopril decreased the value of angiotensin II in blood vessel (P < 0.01). CONCLUSION: HSX decreased the blood pressure significantly for RHHR and the mechanism of its antihypertensive effect was possibly related to the increasing of serum NO and the decreasing of angiotensin II1 in the thoratic aorta.

Critchley J, Liu J, Zhao D, Wei W, Capewell S. · International Health Research Group, Liverpool School of Tropical Medicine, UK. · Circulation. · Pubmed #15337690 links to  free full text

Abstract: BACKGROUND: Coronary heart disease (CHD) mortality is rising in many developing countries. We examined how much of the increase in CHD mortality in Beijing, China, between 1984 and 1999 could be attributed to changes in major cardiovascular risk factors and assessed the impact of medical and surgical treatments. METHODS AND RESULTS: A validated, cell-based mortality model synthesized data on (1) patient numbers, (2) uptake of specific medical and surgical treatments, (3) treatment effectiveness, and (4) population trends in major cardiovascular risk factors (smoking, total cholesterol, blood pressure, obesity, and diabetes). Main data sources were the WHO MONICA and Sino-MONICA studies, the Chinese Multi-provincial Cohort Study, routine hospital statistics, and published meta-analyses. Age-adjusted CHD mortality rates increased by approximately 50% in men and 27% in women (1608 more deaths in 1999 than expected by application of 1984 rates). Most of this increase ( approximately 77%, or 1397 additional deaths) was attributable to substantial rises in total cholesterol levels (more than 1 mmol/L), plus increases in diabetes and obesity. Blood pressure decreased slightly, whereas smoking prevalence increased in men but decreased substantially in women. In 1999, medical and surgical treatments in patients together prevented or postponed approximately 642 deaths, mainly from initial treatments for acute myocardial infarction ( approximately 41%), hypertension (24%), angina (15%), secondary prevention (11%), and heart failure (10%). Multiway sensitivity analyses did not greatly influence the results. CONCLUSIONS: Much of the dramatic CHD mortality increases in Beijing can be explained by rises in total cholesterol, reflecting an increasingly "Western" diet. Without cardiological treatments, increases would have been even greater.

Davis HR, Zhu LJ, Hoos LM, Tetzloff G, Maguire M, Liu J, Yao X, Iyer SP, Lam MH, Lund EG, Detmers PA, Graziano MP, Altmann SW. · Department of Cardiovascular/Metabolic Disease and Department of Discovery Technologies, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. · J Biol Chem. · Pubmed #15173162 links to  free full text

Abstract: Niemann-Pick C1 Like 1 (NPC1L1) is a protein localized in jejunal enterocytes that is critical for intestinal cholesterol absorption. The uptake of intestinal phytosterols and cholesterol into absorptive enterocytes in the intestine is not fully defined on a molecular level, and the role of NPC1L1 in maintaining whole body cholesterol homeostasis is not known. NPC1L1 null mice had substantially reduced intestinal uptake of cholesterol and sitosterol, with dramatically reduced plasma phytosterol levels. The NPC1L1 null mice were completely resistant to diet-induced hypercholesterolemia, with plasma lipoprotein and hepatic cholesterol profiles similar to those of wild type mice treated with the cholesterol absorption inhibitor ezetimibe. Cholesterol/cholate feeding resulted in down-regulation of intestinal NPC1L1 mRNA expression in wild type mice. NPC1L1 deficiency resulted in up-regulation of intestinal hydroxymethylglutaryl-CoA synthase mRNA and an increase in intestinal cholesterol synthesis, down-regulation of ABCA1 mRNA, and no change in ABCG5 and ABCG8 mRNA expression. NPC1L1 is required for intestinal uptake of both cholesterol and phytosterols and plays a major role in cholesterol homeostasis. Thus, NPC1L1 may be a useful drug target for the treatment of hypercholesterolemia and sitosterolemia.

Scholtz CL, Peeters AV, Hoogendijk CF, Thiart R, de Villiers JN, Hillermann R, Liu J, Marais AD, Kotze MJ. · MRC Cape Heart Group, Division of Human Genetics, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa. · Hum Mol Genet. · Pubmed #10484771 links to  free full text

Abstract: The low-density lipoprotein receptor (LDLR) plays a major role in cholesterol homeostasis. Mutations in the regulatory region of the LDLR gene, although rare, have been shown to alter transcriptional activity of the gene and can cause familial hypercholesterolaemia (FH). In this study, a transition (c-->t) was identified at nucleotide position -59 within repeat 2 of the LDLR promoter in a South African FH patient of mixed ancestry. By screening 17 family members of the index case for this promoter mutation, two additional single base changes (-124c-->t and-175g-->t) were identified, located at recently described cis- acting regulatory sequences of the LDLR promoter. Both the-59c-->t and the-124c-->t transitions were identified in the normocholesterolaemic son of the index patient. Reporter plasmids containing the normal and mutant promoter fragments were constructed by directional cloning. Transcription studies using a luciferase reporter system demonstrated that the-59c-->t mutation significantly reduces promoter activity in both the presence and absence of sterols ( approximately 40% of normal activity), while the-124c-->t variant increases transcription ( approximately 160%) of the LDLR gene. The intra-familial phenotypic variability observed amongst individuals with the-59c-->t mutation can probably be ascribed to allelic interaction, suggesting that variation in the LDLR promoter region may contribute significantly to the phenotypic expression of FH-related mutations in populations where these mutations prevail.