Hyperlipidemias: Liu L

Yeh YY, Liu L. · Department of Nutrition, The Pennsylvania State University, University Park, PA 16802, USA. · J Nutr. · Pubmed #11238803 links to  free full text

Abstract: The medicinal use of garlic dates back thousands of years, but there was little scientific support of its therapeutic and pharmacologic properties until recently. In the past decade, the cancer-protective effects of garlic have been well established by epidemiologic studies and animal experiments. However, the cardiovascular-protective properties of garlic are less well understood. In particular, despite the reported hypocholesterolemic effect of garlic, the mechanism of the effect is unclear. In a recent randomized, double-blind, placebo-controlled intervention study, we showed that aged garlic extract (AGE) supplementation was effective in lowering plasma concentration of total cholesterol by 7% and LDL cholesterol by 10% in hypercholesterolemic men compared with subjects consuming a placebo. Supplementation of AGE in animal diets similarly reduced plasma concentrations of total cholesterol and triacylglycerol by 15 and 30%, respectively. In subsequent experiments using cultured rat hepatocytes, we found 44--87% inhibition of cholesterol synthesis by the water-extractable fraction (WEF), methanol-extractable fraction (MEF) and petroleum ether-extractable fraction (PEF) of fresh garlic, and Kyolic (liquid form of AGE). These observations suggested that hydrophilic and hydrophobic compounds of garlic are inhibitory to cholesterol synthesis. Because S-allylcysteine (SAC) alone was less potent than Kyolic, which contains SAC and other sulfur compounds, a maximal inhibition appears to require a concerted action of multiple compounds of garlic. In a series of experiments, we further characterized the inhibitory potency of individual water-soluble and lipid-soluble compounds of garlic. Among water-soluble compounds, SAC, S-ethylcysteine (SEC), and S-propylcysteine (SPC) inhibited cholesterol synthesis by 40--60% compared with 20--35% by gamma-glutamyl-S-allylcysteine (GSAC), gamma-glutamyl-S-methylcysteine (GSMC) and gamma-glutamyl-S-propylcysteine (GSPC). Lipid-soluble sulfur compounds (i.e., diallyl sulfide, diallyl disulfide, diallyl trisulfide, dipropyl sulfide and dipropyl trisulfide) at low concentrations (0.05--0.5 mol/L) slightly (10--15%) inhibited cholesterol synthesis but became highly cytotoxic at high concentrations (1.0--4.0 mol/L). All water-soluble compounds, except S-allylmercaptocysteine, were not cytotoxic, judging from the release of cellular lactate dehydrogenase into the culture medium. Taken together, the results of our studies indicate that the cholesterol-lowering effects of garlic extract, such as AGE, stem in part from inhibition of hepatic cholesterol synthesis by water-soluble sulfur compounds, especially SAC.

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.

Yao P, Song F, Li K, Zhou S, Liu S, Sun X, Nussler AK, Liu L. · Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, China. · Am J Chin Med. · Pubmed #17708630 No free full text.

Abstract: Ginkgo biloba extract (EGB) functions as a natural substantial antioxidant and hypolipidemic. Chronic alcohol abuse leads to sustained dyslipidemia characterized by hyperlipidemia and lipid peroxidation. Thus, the present study investigates the effect of EGB on lipid disorders induced by ethanol in rats. Male Sprague-Dawley rats were fed with ethanol (2.4 g/kg), and pretreated with a daily dose of low or high EGB (48 or 96 mg/kg, respectively). During the experiment, serum was collected on day 30, 60, and 90. Serum lipid profile, including lipid peroxidation, was determined by colorimetric methods. Our data showed that ethanol intake resulted in a time-dependent increase in serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA), and a decrease of the ratio of high-density lipoprotein cholesterol (HDL-C) against TC. EGB prophylactic medication (48 and 96 mg/kg), especially at the high dose, significantly increased HDL-C content, and normalized the abnormal lipid profile and peroxidation in comparison to ethanol-fed only rats. These results suggest that ethanol results in time-dependent hypercholesterolemia, hypertriglyceridemia and promotes serum lipid peroxidation. EGB pretreatment prevents hyperlipidemia and ameliorates lipid peroxidation induced by ethanol.

Zhang L, Zuo L, Xu G, Wang F, Wang M, Wang S, Lv J, Liu L, Wang H. · Division of Nephrology and Institute of Nephrology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, PR China. · Nephrol Dial Transplant. · Pubmed #17210584 links to  free full text

Abstract: BACKGROUND: Chronic kidney disease (CKD) is a public health problem, while data from developing countries are limited. We sought to investigate the epidemiological features of kidney damage in metropolis-residing Chinese adults (>40 years old), and to determine the associated factors of CKD. METHODS: Two thousand three hundred and fifty-three residents in one district of Beijing were interviewed and tested for albuminuria, reduced renal function, haematuria and pyuria. The associations between demographic characteristics, health characteristics and indicators of kidney damage were examined. RESULTS: Albuminuria was detected in 6.2% of subjects; reduced renal function was found in 5.2% of subjects; haematuria was found in 0.8% and non-infective pyuria was found in 0.09%. Approximately, 11.3% (95% confidence interval: 10.0-12.8%) of subjects had at least one indicator of kidney damage. The awareness rate of CKD was only 7.2%. Systolic blood pressure and diabetes were independently associated with albuminuria. Age, diastolic blood pressure, hypercholesteraemia, hypertriglyceridaemia and hyperuricaemia were independently associated with reduced renal function. CONCLUSIONS: This is the first report on the prevalence of CKD in a community-based population within a developing country, determined using protocols recommended by kidney disease improving global outcomes (KDIGO). The prevalence of CKD in our population was close to the levels observed in developed countries, and the spectrum of CKD and associated factors were similar to developed countries. Results from this study suggest that strategies aimed at an intervention of hypertension and other metabolic disorders might prove effective in controlling the pandemic of CKD in China, as well as other developing countries.

Yu H, Fu G, Zhao J, Liu L, He B. · The Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University, Tianjin, PR China. · Artif Cells Blood Substit Immobil Biotechnol. · Pubmed #16893813 No free full text.

Abstract: Poly(acrylic acid) (PAA)-grafted cellulose copolymer beads were synthesized and tested in vitro as an adsorbent for selective removal of low-density lipoprotein (LDL) from human plasma. The copolymers were prepared by graft copolymerization of acrylic acid (AA) onto porous cellulose beads using cerium ammonium nitrate (CAN) as an initiator. The effect of initiator concentration, monomer amount and reaction time on the grafting was examined, and it revealed that the extent of grafting could be controlled by setting the appropriate reaction conditions. In vitro batch-wise adsorption tests were conducted to evaluate the lipoprotein sorption properties of the resulted copolymer beads, and the effect of grafting conditions on the adsorption performance was investigated. It was shown that the binding capacities of the best adsorbent derived from the appropriate reaction conditions could reach 4.96 mg/g total cholesterol (TC) and 4.46 mg/g LDL cholesterol (LDL-C) from human plasma, respectively, without significantly affecting the contents of beneficial constitutes such as high-density lipoprotein (HDL) and total proteins (TP). The influences of plasma amount and adsorption period on the adsorption properties were also determined and analyzed. It appears that this kind of copolymer is worthy of being developed as an alternative LDL adsorbent.

Liu L, Ikeda K, Chen M, Yin W, Mizushima S, Miki T, Nara Y, Yamori Y. · Department of Neurobiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. · Clin Exp Pharmacol Physiol. · Pubmed #15649295 No free full text.

Abstract: 1. The aim of the present study was to investigate the trend of the prevalence of obesity in China and its association with hypertension and hypercholesterolemia. 2. A multicentre cross-sectional study was conducted in Chinese men and women aged 48-56 years between 1985 and 2000. In the report, three study periods were classified as survey 1 (1985), survey 2 (1988-1989) and survey 3 (1997-2000) in order to describe the long-term trend. 3. The results show that: (i) mean body mass index (BMI), prevalence of obesity (BMI > or = 28 kg/m2) and overweight (BMI > or = 25 and < 28 kg/m2) increased significantly from 1985 to 2000 in both sexes (P < 0.001); (ii) similar to the trend for BMI, the prevalence of hypertension and hypercholesterolaemia (total cholesterol (TC) > or = 220 mg/dL) also increased significantly from 1985 to 2000 (P < 0.001); (iii) partial correlation and multiple linear regression analyses indicated that increased BMI was significantly positively correlated with blood pressure and TC and negatively correlated with serum high-density lipoprotein-cholesterol (P < 0.01 or P < 0.001); and (iv) multiple logistics regression analysis models indicated that obese subjects had a 3.9-fold higher risk of being hypertensive (relative risk (RR) 4.9; 95% confidence interval (CI) 3.4-7.3) compared with those subjects who had a BMI less than 25 kg/m2. The corresponding RR (95% CI) of obesity for hypercholesterolaemia was 2.63 (1.57-4.40). 4. In conclusion, the results highlight the epidemic of obesity, an emerging risk in China. Great efforts must be made to alter this unwelcome trend.

Zhao SP, Wu J, Zhang DQ, Ye HJ, Liu L, Li JQ. · Department of Cardiology, The Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 86, Changsha, Hunan 410011, PR China. · Atherosclerosis. · Pubmed #15530897 No free full text.

Abstract: BACKGROUND: CD36 as a fatty acid transporter is predominantly expressed in adipocytes. We studied whether adipocytes could uptake and degrade OxLDL through CD36 and explored the effect of fenofibrate on OxLDL uptake in adipocytes from hypercholesterolemia rabbits. METHODS: Subcutaneous adipose tissues were collected from normal, high-cholesterol and high-cholesterol plus fenofibrate treatment rabbits for adipocytes culture. CD36 and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expression were evaluated by RT-PCR. RESULTS: Cellular expression of CD36 was confirmed during differentiation of adipose cell by RT-PCR. Upon incubation at 37 degrees C, (125)I-OxLDL was endocytosed in a dose-dependent fashion and underwent lysosomal degradation by adipocytes. In binding experiments at 4 degrees C, (125)I-OxLDL exhibited specific and saturable binding to adipocytes (K(D) = 4.2 microg/mL). The endocytic uptake and degradation of (125)I-OxLDL by adipocytes were inhibited by 56 and 54% with anti-CD36 antibody. Fenofibrate treatment enhanced the (125)I-OxLDL uptake and degradation and up-regulated CD36 mRNA expression in adipocytes and suppressed PPARgamma mRNA expression in adipose tissue from hypercholesterolemia rabbits. CONCLUSION: CD36 plays a novel role in adipose tissues and adipocytes possibly involve in clearance of OxLDL in blood. Fenofibrate treatment improved the OxLDL uptake and degradation in adipocytes from hypercholesterolemia rabbits.

Liu L, Cheng Y, Zhang H. · Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Yuquan Campus, Zhejiang University, Hangzhou 310027, China. · Chem Pharm Bull (Tokyo). · Pubmed #15516749 links to  free full text

Abstract: Xue-Fu-Zhu-Yu-Tang is a famous traditional Chinese medicine (TCM) formula for treating cardiovascular disease and related ailments in China for centuries. To profile the phytochemical constituents of the formula, an HPLC-DAD-ESI-MS analytical method has been developed to separate and determinate the medium- or non-polar fraction of the decoction, which has been demonstrated potency to lower the serum total triglyceride concentration, strongly decrease the TXA(2)/PGI(2) ratio and attenuate production of proinflammatory cytokines in high cholesterol-fed rats. By comparing their retention time, UV and MS data with those obtained from the authentic compounds, ferulic acid (1), naringin (2), neohesperindin (3), naringenin (8), marmin (13), senkyunolide A (14), dehydrosafynol (16), safynol (17) and Z-ligustlide (18) are unequivocally determined. Moreover, additional thirteen compounds are tentatively identified as senkyunolide I (4), senkyunolide H (5), poncirin (7), benzoylpaeoniflorin (10), (Z)-6,7-epoxyligustilide (11), senkyunolide G (12), 2-methoxy-safynol (15), cnidilide (19), tangeritin (20), saikosaponin b(2) (21), 29-O-acetylsaikosaponin b(2) (22), saikosaponin b(1) (23) and auraptene (24), according to the comparison of their UV and MS data with the published data. The present study provides an approach to rapidly characterize bioactive constituents in TCM formulae.

Liu L, Zhao SP, Gao M. · Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha 410011, China. · Hunan Yi Ke Da Xue Xue Bao. · Pubmed #12575310 No free full text.

Abstract: OBJECTIVE: To explore the changes of carotid atherosclerosis and the endothelial function after a high-fat meal in elderly patients with coronary artery disease (CAD). METHODS: The carotid intima-media thickness (IMTc) and the brachial artery flow-mediated vasodilation (FMD) before and after a high-fat meal were measured by the high-resolution ultrasound technique in 20 elderly patients with CAD and 22 healthy elderly subjects. RESULTS: The CAD patients had a higher IMTc (P < 0.01) and impaired FMD (P < 0.05) compared with the healthy subjects. The serum triglyceride level increased in the two groups after the meal. The CAD patients had a higher triglyceride peak response (TGPR) than the healthy subjects (P < 0.05). The IMTc of the two groups had no change before and after the meal. The postprandial FMD significantly aggravated in the two groups (P < 0.001); and the percent decrement of FMD in the CAD patients was obviously higher than that in the healthy subjects (P < 0.05). The postprandial TGPR was positively correlated with the fasting IMTc and the postprandial percent decrement of FMD (P < 0.01). CONCLUSION: The disordered postprandial metabolism of triglyceride-riched lipoproteins may play an atherogenic role by inducing endothelial dysfunction.

Negishi H, Njelekela M, Ikeda K, Sagara M, Noguchi T, Kuga S, Kanda T, Liu L, Nara Y, Tagami M, Yamori Y. · Graduate School of Human and Environmental Studies, Kyoto University, Japan. · Hypertens Res. · Pubmed #10821140 No free full text.

Abstract: Oxidative stress has been reported to be involved in not only cardiovascular diseases but in hypertension, which is a major risk for cardiovascular diseases. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been recognized as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. In the present study, we assessed the oxidative stress in human subjects with hypertension and in hypertensive rats. In stroke-prone spontaneously hypertensive rats at the age of 14 weeks, the excretion of urinary 8-OHdG was significantly (p < 0.05) increased compared with that in age-matched normotensive Wistar-Kyoto rats. Next, we investigated the relationship between oxidative DNA damage and cardiovascular risk factors among Tanzanians aged 46-58 years in a population study carried out in 1998 in at Dar es Salaam, Tanzania, according to the WHO-CARDIAC Study Protocol. Sixty subjects (male/female, 28/32) were selected by SPSS Base 8.0 from those who completed a 24-h urine collection. The 24-h urinary 8-OHdG of the hypertensive subjects (SBP > or =140 mmHg and/or DBP > or =90 mmHg) was significantly (p < 0.05) higher than that of the normotensive subjects (SBP <140 mmHg and DBP <90 mmHg) after adjusting for age and gender (Hypertensives: 17.31 +/- 2.0 ng/mg creatinine, n=38; Normotensives: 10.10 +/- 2.64 ng/mg creatinine, n=22). Oxidative stress was thought to be involved in hypertensive subjects and in hypertensive rats.

Pei W, Baron H, Müller-Myhsok B, Knoblauch H, Al-Yahyaee SA, Hui R, Wu X, Liu L, Busjahn A, Luft FC, Schuster H. · Sino-German Laboratory for Molecular Medicine, Fu Wai Heart Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences. · Clin Genet. · Pubmed #10733233 No free full text.

Abstract: We examined familial combined hyperlipidemia (FCHL) families from nonisolated regions in Germany and China to see if we could corroborate support for a chromosome 1q FCHL locus in more general populations. We recruited 24 German families with 137 members, 92 of whom met the criteria of affected in terms of the low density lipoprotein (LDL) and triglyceride levels in excess of the 90th percentile for age and gender. In China, we recruited 12 families with a total of 81 members. All affected persons had total cholesterol concentrations >240 mg/dl and triglyceride concentrations >250 mg/dl. We examined the markers APOA2, D1S1677, D1S104, D1S194, D1S426, and D1S196. Two-point linkage analysis allowing for heterogeneity gave a maximum linkage of disorder score (HLOD) of 2.60 right over D1S194, estimating the proportion of linked families at 36%. This marker is adjacent to D1S104. The evidence for linkage was roughly the same both in the German (HLOD 1.40) and Chinese families (HLOD 1.52). Marker D1S194 is close to the retinoid X receptor (RXR) gene locus, which was found to be linked to triglyceride levels in an earlier twin study from our laboratory. We interpret our observations as encouraging support for the recent findings indicating the presence of a gene for FCHL on chromosome 1q. Furthermore, since DIS194 is adjacent to the gene for the RXR, we suggest that RXR is an attractive candidate for involvement in FCHL.