Hyperlipidemias: China

Chen ZY, Jiao R, Ma KY. · Food and Nutritional Sciences Programme, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, China. · J Agric Food Chem. · Pubmed #18778072 No free full text.

Abstract: Epidemiological studies have demonstrated that elevated levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the major risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) and a low ratio of TC to HDL-C are protective against CHD. A relationship between plasma TC and the risk of CHD is well established at concentrations above 240 mg/dL. In addition to the use of three main classes of cholesterol-lowering medications, including HMG-CoA reductase inhibitors, anion-exchange resins, and fibrates, a nutritionally balanced diet that reduces saturated fat and cholesterol intake has traditionally been the first goal of dietary therapy in lowering plasma TC. In recent years, nutraceuticals and functional foods have attracted much interest as possible alternative therapies for lowering plasma TC, especially for hypercholesterolemia patients, whose blood cholesterol level is marginally high (200-240 mg/dL) but not high enough to warrant the prescription of cholesterol-lowering medications. This review summarizes the findings of recent studies on the production, application, efficacy, and mechanisms of popular cholesterol-lowering nutraceuticals and functional foods.

Wang J, Zhang JS. · Guang' anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. · Zhongguo Zhong Yao Za Zhi. · Pubmed #17672328 No free full text.

Abstract: According to research results of the lipid-lowering Chinese medicine at home and abroad in recent years, the paper will elaborate on the research status of the antihyperlipidemia effects of chinese medicine from the aspects of its vitro screening model, effective monomer, compounding, single medicine and antihyperlipidemia traditional Chinese medicine patent prescription. Put the ideas of development and use on the antihyperlipidemia effects of chinese medicine effective monomer and components medicine compatibility, emphasize on through new medicine screening cell model to find the antihyperlipidemia effects of chinese medicine monomer and antihyperlipidemia mechanism, breakthrough the single mode to use the accumulate of experience in clinical research as the development of new drugs. Study against the changes of the single-ingredient fixed component, the modify of the effective components combination of different drugs, the component compatibility of the different pathological link and the properties of the effective monomer, accelerate the theoretical innovation about the combination of effective medicine monomer, improve the research levels of the medicine combination from pieces to component, make the action target, link, and mechanism of herbal pharmacology more clear, promote the new Chinese herbal research, the improvement of the clinical efficient and the theory innovation of traditional chinese medicine.

Tan KC. · Department of Medicine, University of Hong Kong, Hong Kong. · Cardiovasc Hematol Disord Drug Targets. · Pubmed #17584044 No free full text.

Abstract: The metabolic syndrome consists of a clustering of metabolic derangements that cause the affected individual to have an increased risk for developing cardiovascular disease. Dyslipidemia is an important component of the metabolic syndrome and is included in all the definitions of the metabolic syndrome published by different international committees to identify individuals with the metabolic syndrome. Atherogenic dyslipidemia in the metabolic syndrome comprises of hypertriglyceridemia, low levels of high-density lipoprotein cholesterol and a preponderance of small dense low-density lipoprotein particles. The pathogenesis of dyslipidemia in the metabolic syndrome will be reviewed and the roles of therapeutic lifestyle modification and drug therapies in the treatment of dyslipidemia will be discussed.

Rao K, Du GH, Yang WM. · Department of Urology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. · Zhonghua Nan Ke Xue. · Pubmed #16894947 No free full text.

Abstract: Hyperlipidemia is one of the risk factors leading to erectile dysfunction (ED), a common disorder in men, especially in old men. Epidemiological studies have found that the decrease in high density lipoprotein (HDL) and elevation of total cholesterol/high density lipoprotein (TC/HDL) are correlated with ED. Studies have also shown that arterial stenosis and occlusion caused by hyperlipidemia could be attributed to the advanced-stage mechanism of ED induced by hyperlipidemia. Hyperlipidemia may damage man's erectile function at an early stage by affecting the endothelial cells and smooth muscles of the penis and the peripheral nerves for penile erection. Apart from dietary therapy and drug therapy aiming at hyperlipidemia, the traditional Chinese medicine therapy and gene therapy are two promising approaches to the treatment of ED caused by hyperlipidemia.

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.

Zhou L, Zuo Z, Chow MS. · Faculty of Medicine, School of Pharmacy and Drug Development Centre, Chinese University of Hong Kong, Shatin, N.T. Hong Kong, PR China. · J Clin Pharmacol. · Pubmed #16291709 No free full text.

Abstract: Danshen, the dried root of Salvia miltiorrhiza, has been widely used in China and, to a lesser extent, in Japan, the United States, and other European countries for the treatment of cardiovascular and cerebrovascular diseases. In China, the specific clinical use is angina pectoris, hyperlipidemia, and acute ischemic stroke. The current review covers its traditional uses, chemical constituents, pharmacological activities, pharmacokinetics, clinical applications, and potential herb-drug interactions based on information obtained in both the English and Chinese literature. Although numerous clinical trials have demonstrated that certain Danshen products in China are effective and safe for the treatment of cardiovascular diseases, most of these lack sufficient quality. Therefore, large randomized clinical trials and further scientific research to determine its mechanism of actions will be necessary to ensure the safety, effectiveness, and better understanding of its action.

Chan JC, Tong PC, Critchley JA. · Departmentof Medicine Therapeutics,Prince of Wales Hospital,TheChinese University of Hong Kong Shatin, Hong Kong. · Semin Vasc Med. · Pubmed #16222595 No free full text.

Abstract: For more than a decade, insulin resistance has been proposed as the key linking factor for the metabolic syndrome disease cluster of glucose intolerance, hypertension, dyslipidemia, obesity, and cardiovascular disease. Although most of the epidemiological, experimental, and clinical evidence still support the role of insulin resistance as an important component of this multifaceted syndrome, there is evidence amassing that a neurohormonal mechanism, including an endocrine role for adipocytes, probably plays a more fundamental role. This is supported by the strong associations between obesity, especially central adiposity, and all components of the metabolic syndrome, in contrast to the inconsistent relationships between blood pressure and markers of insulin resistance. However, much of the effect of visceral fat on cardiovascular risk factors is mediated through the metabolic actions of free fatty acids (FFA) on insulin resistance, thus resolving any obesity versus insulin resistance controversy. In addition to the roles of obesity and FFA in the development of insulin resistance syndrome, the high prevalence rates of this disease cluster among subjects from low socioeconomic groups as well as from developing countries have led to alternative hypotheses to better our understanding of the contributory roles of socioeconomic, in utero, and genetic factors in this syndrome. More recently, the pathogenetic roles of iron overload and liver dysfunction have also been re-examined. In this article, the various hypotheses which have been put forward to explain the diverse clinical manifestations of the metabolic or insulin resistance syndrome are summarized and put into perspective. While there is clinical and experimental evidence to support many of these independent pathways, alternative statistical methods such as factor analysis or structural equation modeling may be needed to unravel the complex nature of these interacting pathways. Finally, these hypotheses, if proven, will add new dimensions to our current strategies and emphasize the need to focus on behavioral and socioeconomic interventions in addition to the use of pharmacological therapy in our attempt to control this epidemic disease of modern societies.

Wang LY, Lin J, Liu S, Chen BS. · Beijing Institute of Heart Lung and Blood Vessel Diseases-Beijing Anzhen Hospital, Affiliated of Capital University of Medical Sciences, Beijing 100029, China. · Yi Chuan Xue Bao. · Pubmed #16078748 No free full text.

Abstract: Familial hypercholesterolemia (FH),which is caused by low-density lipoprotein (LDL) receptor mutation, leads to LDL-R dysfunction and high plasma LDL level and early onset of cardiovascular disease. LDL-R mutation has been regarded as the only cause of FH phenotype. However, evidences from recent studies showed that another six gene mutations can also result in FH like phenotype through different mechanism. Further studies on these genes will clarify the mechanism of plasma LDL regulation and provide the molecular basis for the diagnosis and treatment of patients with FH-like phenotype. This review summarizes recent studies on the molecular basis of FH-like phenotype heterogeneity in the hope of drawing more attention to the disease.

Hu Q, Zhang Y. · Department of Cardiology, Qilu Hospital, Shandong University, Jinan 250012, China · Zhonghua Yi Xue Za Zhi. · Pubmed #16061036 No free full text.

This publication has no abstract.

Xu HS, Dai SL, Sun RY. · Department of Pathophysiology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China. · Zhongguo Yi Xue Ke Xue Yuan Xue Bao. · Pubmed #15960278 No free full text.

Abstract: Phytoestrogens are bioactive substances existing in natural plants. They have similar molecular structure to those of estrogens. In this article we introduced their classification and sources, and elucidated their effects on heart from aspects involving cardiac function and myocardial electrophysiology. By regulating serum lipid metabolism, arterial vessels, cytokine levels, and coagulation/fibrinolysis system, phytoestrogens possess the effects of anti-atherosclerosis and may be used to prevent and treat cardiovascular diseases.

Tang T, Li Y. · Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, Beijing 100050. · Sheng Li Ke Xue Jin Zhan. · Pubmed #15881340 No free full text.

Abstract: Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element-binding proteins (SREBPs). SREBPs directly activate the expression of numerous genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, together with the NADPH cofactor required to synthesize these molecules. In this review, we focus on the mechanism of SREBP trafficking and processing, as well as the molecular aspects of SREBPs in regulating cellular lipid homeostasis; furthermore, we discuss the involvement in the diseases relevant to the disturbance of lipid metabolism.

Liu HK, Zhang SZ, Su ZG, Ma YX, Wang CT. · Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu, China. · Yi Chuan. · Pubmed #15640132 No free full text.

Abstract: Using methods of comparative and functional genomics, a new gene coding for apolipoprotein A5 was identified in the vicinity of APOA1/C3/A4 cluster on human chromosome 11q23 by Pennaccio team and Vliet team. The open reading frame of human APOA5 encoded a 366-amino acid protein with high sequence homology to mouse Apoa5 and human APOA4. Mice expressing a human APOA5 transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoa5 had four times as much plasma triglycerides as controls. Single nucleotide polymorphisms (SNPs) in APOA5 (S19W, -1131T>C) and APOA5 haplotype (APOA5*3) were independently associated with high plasma triglyceride levels. These findings indicate that APOA5 is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.

Li XP, Zhao SP. · Department of Cardiology, 2nd Xiangya Hospital, Zhongnan University, Changsha 410011, China · Zhonghua Yi Xue Za Zhi. · Pubmed #15500754 No free full text.

This publication has no abstract.

Liu A, Zhan S, Li L. · Department of Preventive Medicine, the Inner Mongolia Baotou Medical University, Baotuo 014010, China · Zhonghua Liu Xing Bing Xue Za Zhi. · Pubmed #15455471 No free full text.

This publication has no abstract.

Zhang HJ, Zhuang H, Liu XE. · Department of Pathogenic Biology, Medical School, Beijing University, Beijing 100083, China · Zhonghua Liu Xing Bing Xue Za Zhi. · Pubmed #15308049 No free full text.

This publication has no abstract.

Jin N, Wang X. · Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100083. · Sheng Li Ke Xue Jin Zhan. · Pubmed #15127591 No free full text.

Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand-dependant nuclear transcription factors, consisting of three isoforms: alpha,beta/delta and gamma, which form a subfamily of the nuclear receptors superfamily. PPARs play an important role in adipocyte differentiation, energy metabolism, and inflammation. PPARs' effect goes beyond the improvement of insulin resistance in syndrome X (diabetes mellitus, hypertension, obesity and so on). Through recent years' study, it has been demonstrated that PPARs regulate vascular wall directly, which, therefore, decelerate the development of atherosclerosis. In this review, we will look at current trends of PPARs research in their structure, function, and molecular mechanism related to pathogenesis and therapy of atherosclerosis.

Xie N, Wang X, Cai S. · School of Pharmaceutical Science, Beijing Medical University, Beijing 100083 · Zhong Yao Cai. · Pubmed #12920710 No free full text.

This publication has no abstract.

Yin W, Tsutsumi K. · Department of Biochemistry and Molecular Biology, Medical School, Nanhua University, Hengyang 421001, China. · Cardiovasc Drug Rev. · Pubmed #12847564 No free full text.

Abstract: Lipoprotein lipase (LPL) is a rate-limiting enzyme that hydrolyzes circulating triglyceride-rich lipoproteins such as very low-density lipoproteins and chylomicrons. A decrease in LPL activity is associated with an increase in plasma triglycerides (TG) and a decrease in plasma high-density lipoprotein cholesterol (HDL-C). The increase in plasma TG and decrease in plasma HDL-C are risk factors for cardiovascular disease. Tsutsumi et al. hypothesized that elevating LPL activity would cause a reduction of plasma TG and an increase in plasma HDL-C, resulting in protection against the development of atherosclerosis. To test this hypothesis, Otsuka Pharmaceutical Factory, Inc. synthesized the LPL activator NO-1886. NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL mass in rats. NO-1886 also decreased plasma TG concentration and caused a concomitant rise in plasma HDL-C. Long-term administration of NO-1886 to rats and rabbits with experimental atherosclerosis inhibited the development of atherosclerotic lesions in coronary arteries and aortas. Multiple regression analysis suggested that the increase in plasma HDL-C and the decrease in plasma TG protect from atherosclerosis. The atherogenic lipid profile is changed to an antiatherogenic profile by increasing LPL activity, resulting in protection from atherosclerosis. Therefore, the LPL activator NO-1886 or other possible LPL activating agents are potentially beneficial for the treatment of hypertriglyceridemia, hypo-HDL cholesterolemia, and protection from atherosclerosis.

Vanhoutte PM. · Department of Pharmacology, University of Hong Kong, People's Republic of China. · Circ J. · Pubmed #12845177 links to  free full text

This publication has no abstract.

Critchley JA, Zhao HL, Tomlinson B, Leung W, Thomas GN, Chan JC, Cockram CS. · Divisions of Clinical Pharmacology and Endocrinology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China. · Chin Med J (Engl). · Pubmed #11930647 links to  free full text

Abstract: PURPOSE: To review evidence-based management of nephropathy in patients with type 2 diabetes. DATA SOURCES: A literature search (MEDLINE 1966 to 2000) was performed using the key word "diabetic nephropathy". Relevant book chapters were also reviewed. STUDY SELECTION: Well-controlled, prospective landmark studies and expert review articles on diabetic nephropathy were selected. DATA EXTRACTION: Data and conclusions from the selected articles that provide solid evidence to the optimal management of diabetic nephropathy were extracted and interpreted in light of our clinical research experience with many thousands of Hong Kong Chinese patients. RESULTS: Hypertension, long diabetes duration, poor glycaemic control and central obesity are the most important risk factors. Microalbuminuria is a practical marker to predict overt nephropathy in type 2 diabetic patients. Risk factor modification, renal function monitoring and combined therapies are the current integrated approaches to manage patients with diabetic kidney disease. Optimal glycaemic control is the mainstay of treatment but effective antihypertensive therapy is also key to delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have important renoprotective actions independent of their blood pressure lowering actions. CONCLUSIONS: Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Monitoring renal function and screening for microalbuminuria will allow the identification of patients with nephropathy at a very early stage for intervention. Tight glycaemic control and aggressive antihypertensive treatment as well as the use of renin-angiotensin system inhibitors should substantially delay the progression of nephropathy.

Yang TL, Chen MF, Xia X, Luo BL, Li YJ. · Department of Cardiovascular Medicine, Xiang-Ya Hospital, Central South University, Changsha, Hunan 410008, China. · Eur J Clin Pharmacol. · Pubmed #16447050 No free full text.

Abstract: OBJECTIVE: To test whether treatment with fenofibrate decreases asymmetric dimethylarginine (ADMA) level in hypertriglyceridemic individuals. METHODS: In the present study, 45 subjects with hypertriglyceridemia were recruited to receive treatment with fenofibrate (200 mg/d). Serum concentrations of ADMA, malondialdehyde (MDA), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were measured. Endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery was performed. RESULTS: Compared with control, serum levels of ADMA (0.47+/-0.05 micromol/L in control and 0.62+/-0.28 micromol/L in hypertriglyceridemic patients, P<0.01), MDA and TNF-alpha were markedly elevated, and the level of NO was significantly reduced, concomitantly with impaired endothelium-dependent vasodilation in individuals with hypertriglyceridemia. 8-week treatment with fenofibrate significantly reduced the elevated levels of ADMA (0.53+/-0.12 micromol/L, P<0.01), MDA and TNF-alpha, attenuated the decreased level of NO and improved endothelial function. CONCLUSIONS: These results suggest that the beneficial effect of fenofibrate on the endothelium in hypertriglyceridemic individuals may be related to reduction of ADMA level.

Li JJ, Li YS, Chu JM, Zhang CY, Wang Y, Huang Y, Chen J, Yuan JQ, Huang YL. · Department of Cardiology, Fu Wai Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beilishi Road 167, Beijing 100037, People's Republic of China. · Clin Chim Acta. · Pubmed #16343471 No free full text.

Abstract: BACKGROUND: Atherosclerosis has been considered to be an inflammatory process. In addition to its lipid-lowering properties, statin has been shown to decrease the concentrations of inflammatory markers resulting in reduction of cardiovascular events. Emerging data suggest that withdrawal of statin might be associated with increased cardiac events. The mechanism for this phenomenon, however, is still unclear. We investigated whether acute termination of statin treatment could result in rebound of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), in patients with hyperlipidemia. METHODS: Seventeen patients (11 men and 6 women, mean age 51+/-7 years) with hyperlipidemia were given 40 mg/day of pravastatin for 6 weeks. The concentrations of plasma CRP and IL-6 were evaluated before receiving the statin therapy, immediately after 6 weeks of pravastatin therapy, and at days 1, 3 and 7 after withdrawal of pravastatin therapy. The lipid profile was also evaluated at baseline, 6 weeks of therapy, and at day 7 after terminating pravastatin. RESULTS: Pravastatin therapy induced significant reductions in total cholesterol (TC, 6.88+/-0.36 vs. 5.27+/-0.23 mmol/l, p<0.01), low-density lipoprotein (LDL) cholesterol (4.28+/-0.25 vs. 3.06+/-0.14 mmol/l, p<0.01), CRP (0.28+/-0.16 vs. 0.20+/-0.08 mg/l, p<0.01), and IL-6 (8.4+/-0.6 vs. 6.7+/-0.4 pg/dl, p<0.01). Although the TC and LDL-cholesterol did not change during the 7-day period after withdrawal of pravastatin therapy, the concentrations of CRP and IL-6 increased at day 3 (CRP: 0.20+/-0.08 vs. 0.27+/-0.12 mg/l, and IL-6: 6.7+/-0.4 vs. 7.7+/-0.6 pg/dl, p<0.05 respectively) and at day 7 (CRP: 0.20+/-0.08 vs. 0.30+/-0.14 mg/l, and IL-6: 6.7+/-0.4 vs. 8.7+/-0.8 pg/dl, p<0.01 respectively) after withdrawal of pravastatin therapy. No correlation between increase of CRP as well as IL-6 and small changes of LDL-cholesterol concentrations was found after withdrawal of pravastatin therapy at day 7 (r=-0.021 and r=-0.044 respectively, p>0.05 respectively). CONCLUSIONS: 6 weeks after pravastatin therapy could significant modify the lipid profile and decrease the inflammatory markers including CRP and IL-6 in patients with hyperlididemia. Moreover, statin therapy discontinuation could induce a rebound phenomenon of inflammatory response representing an increase in some inflammatory markers, which is independent of changes of lipid parameters.

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.

Zhao SP, Liu L, Cheng YC, Shishehbor MH, Liu MH, Peng DQ, Li YL. · Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, PR China. · Circulation. · Pubmed #15313947 links to  free full text

Abstract: BACKGROUND: Endothelial dysfunction is associated with inflammation and postprandial hypertriglyceridemia. Xuezhikang, an extract of Cholestin, a dietary supplement, has lipid-modulating and antiinflammatory effects. We explored the effects of xuezhikang on endothelial function and high-sensitivity C-reactive protein (hs-CRP) in patients with coronary heart disease (CHD). METHODS AND RESULTS: We prospectively randomized 50 CHD patients to xuezhikang 1200 mg/d or placebo for 6 weeks. Fasting hs-CRP concentrations, flow-mediated vasodilation (FMD) at 0 and 4 hours, and lipid parameters at 0, 2, 4, and 6 hours were monitored after a high-fat meal (800 calories; 50 g fat) in all patients. All patients underwent a high-fat meal test at the beginning of the study and after 6 weeks of treatment. Postprandial FMD was significantly worse at 4 hours after a high-fat meal (P<0.05), and this was associated with the area under the triglyceride curve (TG-AUC) (r=0.345, P<0.01). After 6 weeks of xuezhikang, fasting hs-CRP levels and TG-AUC (P<0.001 for each) decreased. Furthermore, preprandial and postprandial FMD significantly improved (P<0.001). There were no significant changes in serum lipids and FMD in the placebo arm. In multivariable regression analysis, changes in TG-AUC and fasting hs-CRP levels were predictive of improvement in preprandial FMD (P<0.05). CONCLUSIONS: Xuezhikang effectively improved preprandial and postprandial endothelial function through its potent antiinflammatory and lipid-lowering effects.