Hyperlipidemias: Zhang Y

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.

Zhang Y, Donohue JM, Lave JR, O'Donnell G, Newhouse JP. · Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, PA 15261, USA. · N Engl J Med. · Pubmed #19571283 No free full text.

Abstract: BACKGROUND: It is not known what effect the increased use of prescription drugs by enrollees in Medicare Part D has had on spending for other medical care. METHODS: We compared spending for prescription drugs and other medical care 2 years before the implementation of Part D in January 2006 with such expenditures 2 years after the program's implementation in four groups of elderly beneficiaries: Medicare Advantage enrollees with stable, uncapped, employer-based drug coverage throughout the study period (no-cap group), those who had no previous drug coverage, and those who had previous limited benefits (with either a $150 or a $350 quarterly cap) before they were covered by Part D in 2006. RESULTS: Between December 2005 and December 2007, as compared with the increase in the no-cap group, the increase in total monthly drug spending was $41 higher (95% confidence interval [CI], $33 to $50) (74%) among enrollees with no previous drug coverage, $27 higher (95% CI, $20 to $34) (27%) among those with a previous $150 quarterly cap, and $13 higher (95% CI, $8 to $18) (11%) among those with a previous $350 cap. The use of both lipid-lowering and antidiabetic medications rose in the groups with no or minimal previous drug coverage. As compared with expenditures in the no-cap group, monthly medical expenditures (excluding drugs) were $33 lower (95% CI, $29 to $37) in the group with no previous coverage and $46 lower (95% CI, $29 to $63) in the group with a previous $150 quarterly cap, whereas medical spending was $30 higher (95% CI, $25 to $36) in the group with a previous $350 cap. CONCLUSIONS: Enrollment in Medicare Part D was associated with increased spending on prescription drugs. Groups that had no or minimal drug coverage before the implementation of Part D had reductions in other medical spending that approximately offset the increased spending on drugs, but medical spending increased in the group that had more generous previous coverage.

Qu HY, Xiao YW, Jiang GH, Wang ZY, Zhang Y, Zhang M. · The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, No. 107#, Jinan, Shandong, 250012, China. · Pharm Res. · Pubmed #19082693 No free full text.

Abstract: PURPOSE: To compare the short-term effect of treatment with atorvastatin and rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. METHODS: Sixty-nine patients with hypercholesterolemia were randomly assigned to receive 10 mg/day of atorvastatin or rosuvastatin for 12 weeks. Inflammatory biomarkers, including highsensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-9 (MMP-9), and endothelin (ET-1), plasminogen activator inhibitor type 1 (PAI-1) and plasma tissue plasminogen activator (tPA), adiponectin, and lipid profiles were measured before and after statin therapy. RESULTS: Atorvastatin and rosuvastatin both lowered levels of hs-CRP, MMP-9, PAI-1, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) from baseline values, with rosuvastatin lowering TC and LDL-C to a greater extent than atorvastatin (P < 0.05). Adiponectin level increase was 15% higher than that at baseline with atorvastatin (P > 0.05) but 67% higher with rosuvastatin (P < 0.05). CONCLUSIONS: Therapy with both statins not only significantly improved lipid profiles but also decreased levels of vascular biomarkers hs-CRP, MMP-9, and PAI-1; however, only rosuvastatin increased serum adiponectin levels significantly in patients with hypercholesterolemia, which could imply a beneficial effect in coronary artery disease.

Xie W, Zhang Y, Wang N, Zhou H, Du L, Ma X, Shi X, Cai G. · Laboratory of Life Sciences & Marine Biology, Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China. · Eur J Pharmacol. · Pubmed #18930725 No free full text.

Abstract: Macrostemonoside A, a newly found compound, is derived from Allium macrostemon Bung. However, investigation into its nature is lacking. In this study, the effects of macrostemonoside A on hyperglycemia, hyperlipidemia, visceral fat accumulation, and related enzyme activities in high-fat diet-fed C57BL/6 mice are examined. The results showed that mice fed with a high-fat diet had a significant increase in fasting blood glucose, liver glycogen, serum total cholesterol, and visceral fat accumulation, but were mildly or moderately inhibited by macrostemonoside A at a dose of 4 mg/kg/d after 30 days of treatment. This hypoglycemic effect might be associated with the potential increase in insulin sensitivity and visfatin expression, although it needs further validation in future studies. Its anti-obesity effect might be associated with elevated total lipase activity in visceral adipose cells. The up-regulation in the expression of peroxisome proliferators-activated receptor gamma 2 might be responsible for the increased lipase activity in visceral adipose cells. Furthermore, we supposed that its action mechanisms might promote energy metabolism in muscles. Macrostemonoside A, with its steroid-like structure, has no significant cortisone-like side effects on the immune system but has potential cardiovascular protective effects. These results suggested that a potential compound to treat hyperglycemia, hyperlipidemia, and visceral obesity could be developed. However, its underlying mechanisms need further investigation in future studies.

Zhang Y, Xie ML, Xue J, Gu ZL. · Department of Pharmacology, Medical School of Soochow University, Suzhou, China. · J Asian Nat Prod Res. · Pubmed #18696335 No free full text.

Abstract: Osthole (1), an active constituent isolated from Cnidium monnieri (L.) Cusson, has been used in the treatment of diseases for many years in clinical. The aim of this present study was to determine the effect of 1 on protein expression of PPARalpha/gamma and related target molecules such as CYP7A and DGAT protein expression in the liver of hyperlipidemic fatty liver (HFL) rats, and to investigate the possible mechanism of treating HFL.

Zhou Y, Zhang X, Chen L, Wu J, Dang H, Wei M, Fan Y, Zhang Y, Zhu Y, Wang N, Breyer MD, Guan Y. · Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Rd., Beijing, China. · Am J Physiol Renal Physiol. · Pubmed #18614621 No free full text.

Abstract: Hyperlipidemia is one of the major features of nephrotic syndrome (NS). Although many factors have been implicated in the pathogenesis of NS-related dyslipidemia, the underlying mechanisms remain largely uncharacterized. The present study was designed to examine the gene profile associated with lipid metabolism in the livers of nephrotic rats. NS was created in male Sprague-Dawley rats (n = 6) receiving sequential intraperitoneal injections of puromycin aminonucleoside. Analysis by Affymetrix assay, quantitative RT-PCR, and Northern and Western blotting revealed 21 genes associated with cholesterol and fatty acid metabolism. Eight genes involved in cholesterol metabolism, Apo A-I, Acly, Acat, Mpd, Fdps, Ss, Lss, and Nsdhl, were significantly upregulated under NS. Four genes involved in fatty acid biosynthesis, Acc, FAS, ELOVL 2, and ELOVL6, and three critical for triglyceride biosynthesis, Gpam, Agpat 3, and Dgat 1, were significantly upregulated, whereas two genes involved in fatty acid oxidation, Dci and MCAD, were downregulated. Expression of several genes in sterol-regulatory element-binding protein (SREBP)-1 activation was also aberrantly altered in nephrotic livers. The expression and transcriptional activity of SREBP-1 but not SREBP-2 were increased in nephrotic rats as assessed by real-time PCR, immunoblotting, and gel shift assays. The upregulation of hepatic genes involved in cholesterol biosynthesis may play an important role in the pathogenesis of hypercholesterolemia, whereas upregulation of genes participating in hepatic fatty acid and triglyceride biosynthesis and downregulation of genes involved in hepatic fatty acid oxidation may contribute to hypertriglyceridemia in nephrotic rats. Activation of SREBP-1 transcription factor may represent an underlying molecular mechanism of hyperlipidemia in NS.

Xiao C, Watanabe T, Zhang Y, Trigatti B, Szeto L, Connelly PW, Marcovina S, Vaisar T, Heinecke JW, Lewis GF. · Department of Medicine and Physiology, University of Toronto, Ontario, Canada. · Circ Res. · Pubmed #18556574 links to  free full text

Abstract: A low level of high-density lipoprotein (HDL) cholesterol is characteristic of insulin resistance and hypertriglyceridemia and likely contributes to the increased risk of cardiovascular disease associated with these conditions. One pathway involves enhanced clearance of lipolytically modified HDL particles, but the underlying mechanisms remain poorly understood. Here, we examine the effect of triglyceride enrichment and hepatic lipase hydrolysis on HDL binding, internalization, and degradation in cultured liver and kidney cells. Maximal binding of remnant HDL (HDL enriched with triglycerides followed by hepatic lipase hydrolysis), but not binding affinity, was markedly higher than native and triglyceride-rich HDL in both HepG2 cells and HEK293 cells. Compared with native and triglyceride-rich HDL, remnant HDL was internalized to a greater extent in both cell types and was more readily degraded in HEK293 cells. The increased binding of remnant HDL was not mediated by the low-density lipoprotein receptor or scavenger receptor class B type I (SR-BI), because enhanced remnant HDL binding was observed in low-density lipoprotein receptor-deficient cells with or without SR-BI overexpression. Disruption of cell surface heparan sulfate proteoglycans or blockage of apolipoprotein E-mediated lipoprotein binding also did not abolish the enhanced remnant HDL binding. Our observations indicate that remodeling of triglyceride-enriched HDL by hepatic lipase may result in enhanced binding, internalization, and degradation in tissues involved in HDL catabolism, contributing to rapid clearance and overall lowering of plasma HDL cholesterol in insulin resistance and hypertriglyceridemia.

Xing Y, Yue P, Sun LH, Zhao WX, Wang Y, Zhang Y, Liu X, Lu YJ, Yang BF. · Department of Pharmacology, Bio-pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin Medical University, Harbin 150086, China. · Zhongguo Zhong Yao Za Zhi. · Pubmed #17966361 No free full text.

Abstract: OBJECTIVE: To find the molecular mechanism of decreasing blood fat effect of Darning capsule on hyperlipemic rat, we study the expression of connexin43 in the myocardium before and after using the capsule. METHOD: Forty Wistar rats were randomly divided into 5 group: control group, hyperlipemia model group, Daming capsule group of high dose, middle dose and low dose (200, 100, 50 mg kg(-1) d(-1)). Each group had 8 rats. Hyperlipemic rat model was made firstly, the blood was obtained via vena caudalis and the indexes of TC, TG, LDL, HDL and NEFA in the serum were measured. The myocardial total RNA was extracted by Trizol method. To compare the expression of connexin43 in the following groups: hyperlipemia, normal and drug, we used the technique of RT-PCR, immunostaining and microconfoul. RESULT: The concentrations of TC, TG, LDL and NEFA in hyperlipemic serum were increased (P <0. 05), while that of HDL was decreased (P <0. 05). After treating with Daming capsule, the concentration of the preceding four indexes were decreased and the concentrations of HDL was increased up to nearly normal level. No significant difference was found in the ECG of the three groups. As compared with the normal group, the mRNA expressions of connexin43 in hyperlipemia group was weakened (P <0.05), while that of the drug group was enhanced(P <0.05). The same result in immunostaining was observed. CONCLUSION: Hyperlipemic rat model was successfully established and Daming capsule has the effect of lowering blood lipid. Furthermore, the molecular mechanism of Darning capsule is related with the change of Cx43 closely.

Kang Y, Li M, Yan W, Li X, Kang J, Zhang Y. · College of Life Science, Sichuan University, Chengdu, Sichuan, 610064, PR China. · Biotechnol Lett. · Pubmed #17704895 No free full text.

Abstract: Acupuncture or electroacupuncture (EA) is effective in treating various metabolism disorders. Previously we found that EA at the acupoint, Fenglong (ST40), had the cholesterol-lowering effect and regulated genes expression in liver of hypercholesterolemia mice (M Li and YZ Zhang, Int J Mol Med 2007, 19: 617-629). To explain gene expression associated with EA, suppression subtractive hybridization (SSH), combined with targeted display (TD), was used and 26 up-regulated and 24 down-regulated genes with known functions were identified in hypercholesterolemia mice liver, some of which are involved in key reactions of lipid metabolism and immune reaction. Promoting lipid metabolism and suppressing inflammation via modulating mRNA expression may be the mechanism of EA inducing modulation of cholesterol concentrations.

Zhang Y, He X, Chen X, Ma H, Liu D, Luo J, Du Z, Jin Y, Xiong Y, He J, Fang D, Wang K, Lawson WE, Hui JC, Zheng Z, Wu G. · Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China. · Circulation. · Pubmed #17620513 links to  free full text

Abstract: BACKGROUND: Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing shear stress. Chronic exposure of vascular endothelial cells and vascular smooth muscle cells to relatively high physiological shear stress has antiproliferative and vasoprotective effects. The present study hypothesizes that EECP inhibits intimal hyperplasia and atherogenesis by modifying shear stress-responsive gene expression. METHODS AND RESULTS: Thirty-five male pigs were randomly assigned to 3 groups: high-cholesterol diet (n=11), high-cholesterol diet plus EECP (n=17), and usual diet (control; n=7). The coronary arteries and aortas were collected for histopathological study and immunohistochemical and Western blot analysis. The peak diastolic arterial wall shear stress during EECP increased significantly compared with before EECP (49.62+/-10.71 versus 23.92+/-7.28 dyne/cm2; P<0.001). Intimal hyperplasia was observed in the coronary arteries of the high-cholesterol diet group, whereas in animals receiving EECP, the intima-to-media area ratio was significantly decreased by 41.59% (21.27+/-10.00% versus 36.41+/-16.69%; P=0.008). Hypercholesterolemia attenuated the protein expression of endothelial NO synthase and enhanced the phosphorylation of extracellular signal-regulated kinases 1/2. EECP treatment alleviated these adverse changes. CONCLUSIONS: EECP reduces hypercholesterolemia-induced endothelial damage, arrests vascular smooth muscle cell proliferation and migration, decreases proliferating cell nuclear antigen proliferative index, suppresses extracellular matrix formation, and eventually inhibits intimal hyperplasia and the development of atherosclerosis by increasing the arterial wall shear stress, which in turn activates the endothelial NO synthase/NO pathway and probably suppresses extracellular signal-regulated kinases 1/2 overactivation.

Li X, Zhang Y, Yan W, Kang J, Kang Y, Lie M. · College of Life Science, Sichuan University, Sichuan Key Laboratory of Molecular Biology and Biotechnology, Chengdu 610064, P R China. · Acupunct Electrother Res. · Pubmed #17608063 No free full text.

Abstract: We have shown that electroacupuncture (EA) at Fenglong acupoint (ST40) has the cholesterol-lowering effect in hypercholesterolemia mice. The present study was designed to study preventive effect of EA at ST40 on hypercholesterolemia. C57BL/6j mice were randomly divided into normal group (NG), hypercholesterolemia group (HG) and EA prevention group (EPG). NG were fed chow, HG a hypercholesterolemic diet (HD), and EPG the same HD and received EA treatment simultaneously. Lipid profile of both the plasma and liver indicated that EA at ST40 had preventive effect on hypercholesterolemia. Compared with corresponding values in the HG mice, the levels of the hepatic total cholesterol and total triglyceride in the EPG mice lowered 45% and 23% respectively, and the levels of plasma total-, LDL-, and HDL-cholesterol in the EPG mice lowered 39%, 37% and 39% respectively. Eleven genes whose expressions were up-regulated in EPG mice compared with HG were isolated using suppression subtractive hybridization (SSH) combined with negative subtraction chain (NSC) technology, and then confirmed by dot-blot assay. Except two genes whose functions were still unknown, the others were mainly involved in cholesterol metabolism, lipid metabolism, glucose metabolism and immune response. The potential molecular mechanism of preventive effect was discussed.

Prasan AM, McCarron HC, Zhang Y, Jeremy RW. · Department of Medicine, University of Sydney, Sydney, NSW 2006, Australia. · Heart Lung Circ. · Pubmed #17420156 No free full text.

Abstract: AIMS: Nitric oxide (NO) may modulate myocardial ischaemia/reperfusion (I/R) injury, but effects of hypercholesterolaemia on myocardial NO release during I/R are unknown. METHODS: A NO-specific carbon fibre electrode continuously measured coronary sinus [NO] during 60 min low-flow ischaemia (1 ml/min) and 60 min free reperfusion (I/R) in isolated rabbit hearts. Experimental groups (n=7 per group) were control, L-arginine supplement (200 microM), N-nitro-L-arginine methyl ester (L-NAME) treatment (8 microM) and hypercholesterolaemic. RESULTS: During early I, NO release decreased markedly in control (-1356+/-286 pmol/min/g) and L-arginine (-1972+/-172) groups, but less in L-NAME (-441+/-89) and hypercholesterolaemic (-602+/-164) groups (both p<0.01 vs. controls). No increase in NO release during I was seen in any group. After R, NO release increased above baseline in control (+2333+/-591 pmol/min/g) and L-arginine (+1048+/-278) groups and hypercholesterolaemic (+1100+/-478) (p<0.05 vs. pre-ischaemia each group). There was little increase in NO release in the L-NAME group (+436+/-247 pmol/min/g, p<0.05 vs. controls). In each group, myocardial NO release declined towards pre-ischaemic levels during 60 min R. Hearts treated with L-arginine had similar NO release but better functional recovery than controls (p<0.01). Treatment with L-NAME was also associated with better functional recovery than in controls or hypercholesterolaemic hearts. CONCLUSION: Myocardial NO release declines rapidly during ischaemia, but increases above baseline during early reperfusion. Improved function after L-arginine treatment appears to be independent of effects upon NO release. Hypercholesterolaemia is associated with reduced myocardial NO release, under both baseline conditions and during ischaemia and reperfusion.

Li M, Zhang Y. · Sichuan Key Lab of Molecular Biology and Biotechnology, College of Life Science, Sichuan University, Chengdu 610064, P.R. China. · Int J Mol Med. · Pubmed #17334637 No free full text.

Abstract: The aim of this study was to demonstrate the cholesterol-lowering effect of electroacupuncture (EA) at the acupoint of Fenglong (ST40) in mice and to investigate its molecular mechanism by using genome-wide gene expression profile analysis. Mice with hypercholesterolemia induced by a high-cholesterol diet were randomly divided into EA at ST40 group (EG), EA at non-acupoint group (ENG), and simvastatin group (DG). A lipid profile of both the plasma and liver indicated that EA at ST40 had the same hypocholesterolemic effect as that of simvastatin, while EA at non-acupoint failed to produce the same effect. The global gene expression profile showed that EA at ST40 not only regulated the expression of genes which were directly involved in the cholesterol metabolism in the liver, but also significantly affected the expression of genes involved in signal transduction, transcription regulation, cell cycle, cell adhesion, immunity and stress. The gene expression pattern was further verified by real-time RT-PCR. The mechanism by which EA at ST40 regulated liver cholesterol metabolism is discussed. We conclude that the hypocholesterolemic effect is specific to EA at ST40 and not due to general electrical stimulation of muscles. The comprehensive gene expression profile analysis appears particularly useful in the search for EA-induced changes in cholesterol regulation.

Xie W, Nie Y, Du L, Zhang Y, Cai G. · Life Sciences Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China. · Pharmacol Res. · Pubmed #17306985 No free full text.

Abstract: High-fat diets and oxidative damage may contribute to the development of type 2 diabetes. Hypolipidaemic drugs and antioxidants were supposed to prevent the development of the disease. In this study, we investigated preventive effects of fenofibrate (200 mg kg(-1)), vitamin C (30 mg kg(-1)), combination of both in mice induced by streptozotocin (35 mg kg(-1)) and soluble lard (15 ml kg(-1)). The results showed the mice demonstrated hyperglycaemia and hypercholesterolaemia, visceral fat accumulation, and a slight increase in liver glycogen/triglyceride and oxidative stress within 60 days of treatment. Fenofibrate enhanced insulin sensitivity, improved glycaemic control, lowered serum triglycerides, reduced body and visceral fat weights, and decreased liver glycogen/lipid levels but showed hepatotoxicity in the mice. Vitamin C neither itself prevented nor enhanced preventive effects of fenofibrate on glucose and lipid metabolism but partly attenuated the hepatotoxicity of fenofibrate. These results suggest that fenofibrate inhibit development of type 2 diabetes induced by high-fat diets and oxidative stress. However, here, vitamin C just can serve as an adjunct to fenofibrate therapy against its hepatotoxicity. In the future study, we should investigate if higher dosage of vitamin C or other antioxidants would enhance preventive effects of fenofibrate in type 2 diabetes.

Zhang Y, Xie ML, Zhu LJ, Gu ZL. · Department of Pharmacology, Medical School of Soochow University, Suzhou 215123, China. · Acta Pharmacol Sin. · Pubmed #17303003 links to  free full text

Abstract: AIM: To study the effects of osthole on hyperlipidemic fatty liver and investigate the possible mechanisms. METHODS: A rat model with hyperlipidemic fatty liver was successfully established by feeding fatty milk for 6 weeks. The experimental rats were then treated with 5-20 mg/kg osthole for 6 weeks. The mouse hyperlipidemic model was induced by feeding fatty milk when they were treated with 10-20 mg/kg osthole for 3 weeks. RESULTS: After treatment with osthole, the levels of rat serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol significantly decreased as compared with the fatty liver model group (P< 0.05 or P< 0.01). Hepatic weight and its coefficient, the hepatic tissue contents of TC, TG, and malondialdehyde, also significantly decreased (P< 0.05 or P< 0.01). In fatty milk-induced hyperlipidemic mice, the post-heparin plasma activities of lipoprotein lipase (LPL), hepatic lipase (HL), and total lipase (TL) significantly increased after treatment with 10-20 mg/kg osthole for 3 weeks (P< 0.05 or P< 0.01). Importantly, the histological evaluation of rat liver demonstrated that osthole dramatically decreased lipid accumulation (P< 0.01). CONCLUSION: Osthole was found to have therapeutic effects on fatty milk-induced rat fatty liver; the mechanisms might be associated with its anti-oxidation and the elevation of the activities of LPL and HL.

Zhou P, Zhang Y, Xi L, Atahan, Ge J, Yerken, Zhu DL. · Department of Endocrinology, Gulou Hospital, Medical College, Nanjing University, Nanjing 210008, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #16780679 No free full text.

Abstract: OBJECTIVE: To study the serum triglyceride (TG) distribution characteristics and their relation with abnormal glucose metabolism in populations of different nationalities in Ili Prefecture of Xinjiang Uygur Autonomous Region to provide a basis for extending the prevention and treatment of abnormal glucose metabolism. METHODS: With stratified cluster sampling method, epidemiological survey was conducted together with tests blood lipid and abnormal blood glucose metabolism among the permanent resident populations of six major nationalities, i.e Kazak, Uygur, Han, Hui, Xibe and Mongolia; they account for 96.8% of the total population in Ili Prefecture. In the meantime of conducting questionnaire survey and physical examination, blood glucose and blood lipid levels of the surveyed subjects were examined. RESULTS: Among all the people surveyed in Ili Prefecture, the prevalence of hypertriglyceridemia was 36.10%, being higher in urban than in rural areas and higher in males than females (P < 0.001). The prevalence of hypertriglyceridemia in Uygur and Han people (51.73% and 46.56%) was higher than that of Kazak and Mongolian people (16.39% and 18.42%). The prevalence of hypertriglyceridemia increased with the increase of age to different extent (RR value: 1.10 - 2.48). The prevalence of abnormal glucose metabolism also increased with the increase of blood TG levels. CONCLUSION: The levels of serum triglyceride in the population of different nationalities in Ili Prefecture are different in different nationalities, areas, ages and sexes. In those with hypertriglyceridemia, the prevalence of abnormal glucose metabolism increases also.

Lee ET, Howard BV, Wang W, Welty TK, Galloway JM, Best LG, Fabsitz RR, Zhang Y, Yeh J, Devereux RB. · Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190, USA. · Circulation. · Pubmed #16769914 links to  free full text

Abstract: BACKGROUND: The present article presents equations for the prediction of coronary heart disease (CHD) in a population with high rates of diabetes and albuminuria, derived from data collected in the Strong Heart Study, a longitudinal study of cardiovascular disease in 13 American Indian tribes and communities in Arizona, North and South Dakota, and Oklahoma. METHODS AND RESULTS: Participants of the Strong Heart Study were examined initially in 1989-1991 and were monitored with additional examinations and mortality and morbidity surveillance. CHD outcome data through December 2001 showed that age, gender, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, hypertension, and albuminuria were significant CHD risk factors. Hazard ratios for ages 65 to 75 years, hypertension, LDL cholesterol > or = 160 mg/dL, diabetes, and macroalbuminuria were 2.58, 2.01, 2.44, 1.66, and 2.11 in men and 2.03, 1.69, 2.17, 2.26, and 2.69 in women, compared with ages 45 to 54 years, normal blood pressure, LDL cholesterol <100 mg/dL, no diabetes, and no albuminuria. Prediction equations for CHD and a risk calculator were derived by gender with the use of Cox proportional hazards model and the significant risk factors. The equations provided good discrimination ability, as indicated by a c statistic of 0.70 for men and 0.73 for women. Results from bootstrapping methods indicated good internal validation and calibration. CONCLUSIONS: A "risk calculator" has been developed and placed on the Strong Heart Study Web site, which provides predicted risk of CHD in 10 years with input of these risk factors. This may be valuable for diverse populations with high rates of diabetes and albuminuria.

Zhang Y, He XH, Chen XL, Hu RD, Ma H, Wu GF, He JG, Zhan CY, Jin YF, Fang DQ, Zheng ZS. · Key Laboratory of Assisted Circulation, Cardiovascular Research Institute, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. · Zhonghua Bing Li Xue Za Zhi. · Pubmed #16630505 No free full text.

Abstract: OBJECTIVE: To study the effects of enhanced external counterpulsation (EECP) on the vascular morphology, and endothelial function using experimentally induced hypercholesterolemic pigs. METHODS: Thirty five male pigs were randomly divided into three groups: 7 normal control animals, 11 hypercholesterolemic animals, and 17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured. The coronary arteries and aortas were sampled for histopathologic and ultrastructural examination. The NF-kappaB protein expression of porcine coronary arteries was investigated by immunofluorescence. RESULTS: Compared with the normal controls, serum cholesterol levels were significantly higher in the hypercholesterolemic animals with or without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP [(3.33 +/- 2.40)%, versus (12.03 +/- 7.12)% in those without EECP, P < 0.05]. Lipid deposition, endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those not. Moreover, activation and expression of NF-kappaB also decreased significantly (P < 0.05) in animals receiving EECP. CONCLUSIONS: EECP improves the morphology and function of vascular endothelium, and retards the development and progression of atherosclerosis, likely through the inhibition of NF-kappaB signaling pathway.

Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA. · Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA. · Proc Natl Acad Sci U S A. · Pubmed #16410358 links to  free full text

Abstract: Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus.

Chen XL, He XH, Zhang Y, Qian YT, Liang LG, Fang DQ, Zhan CY, Zheng ZS, Ma H. · Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510089, China. · Di Yi Jun Yi Da Xue Xue Bao. · Pubmed #16354613 links to  free full text

Abstract: OBJECTIVE: To verify whether chronic enhanced external counterpulsation (EECP) may repair artery endothelial cells (ECs) damage resulted from hypercholesteremia in pigs. METHODS: EECP was performed for 36 hours in pigs with hypercholesteremia and the left descending artery (LDA) was isolated for scanning electron microscopy (SEM). The ECs were collected from the thoracic aorta and analyzed by proteomic technique. RESULTS: The ECs of hypercholesteremia pigs showed irregular arrangement with obvious desquamation of coronary ECs and formation of atherosclerotic plaque, and these lesions were milder in EECP-treated pigs. Six over-expressed proteins were detected in the endothelial cells in EECP-treated pigs in comparison with those of the hypercholesteremia pigs. CONCLUSION: Chronic EECP helps restore cell morphology and repair functional damage of ECs resulted from hypercholesteremia by regulating endothelial protein expressions, and consequently improves cell adhesion and intracellular metabolism and reduces EC apoptosis.

Qin J, Han TQ, Fei J, Jiang ZY, Zhang Y, Yang SY, Jiang ZH, Cai XX, Huang W, Zhang SD. · Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai Institute of Digestive Surgery, Shanghai 200025, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #16313772 No free full text.

Abstract: OBJECTIVE: To explore the role of both inheritable and epidemiological factors in the pathogenesis of familial gallstone disease in pedigrees. METHODS: 135 pedigrees, with 695 members aged > or = 18 (18 - 83, with a mean of 50 +/- 14), 282 males and 413 females, including 370 patients, at least one patient existing in every generation, were investigated. Inquiry was carried out to collect the personal and medical history. Physical examination and ultrasonography were conducted. Blood samples were collected to detect the total cholesterol (TCh), triglyceride (TG), high-density lipoprotein cholesterol (HDL-Ch), and apolipoprotein (Apo) A1 and ApoB. The concentration of low-density lipoprotein cholesterol (LDL-Ch) was calculated by the formula: Tch-TG/5 + HDL-Ch. The inheritable characteristics and heritability were analyzed. RESULTS: The prevalence of gallstone disease was 53.24%, 56.66% among the females, significantly higher than that among the males (48.23%, P = 0.03). The heritability in the first-degree relatives was 138% +/- 7%, and the concordance rate of monozygotic twins was 100%. The significant risk factors were female gender (P = 0.03), body mass index (P < 0.01) and diet (P < 0.008). The history of hypertension, hyperlipidemia, and diabetes were correlated to gallstone disease (P = 0.008, < 0.008, and 0.03 respectively). Serum HDL-Ch and ApoA1 concentrations were lower in the stone group than in the non-stone group (P = 0.003 and 0.005 respectively). There were no significant differences in TCh, TG, LDL-Ch, and ApoB between the 2 groups. CONCLUSION: Genetic factors play a major role in the pathogenesis of familial gallstone disease, characterized by autosomal dominant inheritance. Female gender, obesity, diet, hypertension, hyperlipidemia, diabetes may be the risk factors of gallstone disease. Dyslipidemia is a characteristic of gallstone disease.

Tao J, Tu C, Yang Z, Zhang Y, Chung XL, Ma H, Zhen ZS. · Department of Cardiology, The First Affiliated Hospital, Sun-Yat Sen University, Guangzhou 510080, China. · Int J Cardiol. · Pubmed #16310261 No free full text.

Abstract: BACKGROUND: Enhanced external counterpulsation (EECP) has been demonstrated to be an effective method for the treatment of atherosclerotic vascular disease. However, the exact mechanism underlying the beneficial effects of EECP is not completely clear. We hypothesized that EECP leads to improvement in endothelial function, contributing to its clinical benefits. METHODS: Fifteen male domestic pigs were initially divided into 2 dietary groups: one consumed a normal feeding (NF) of pig chow (n=5), and one consumed a high-fat (HF) pig chow (n=10). After 8 weeks on the NF or HF diet, 5 HF pigs received EECP treatment (HF+EECP) 1 h daily for 6 weeks and the remaining 5 HF pigs continued to be fed by high cholesterol diet. At the end of 6-week EECP treatment, the carotid arterial rings from all of the pigs were harvested. Endothelium-dependent and -independent vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured in a dose-dependent manner. RESULTS: The high fat diet resulted in increase in plasma cholesterol and triglyceride levels (p<0.05). Endothelium-dependent vasorelaxation was decreased in the HF group compared to the NF control (p<0.05). However, EECP treatment partially improved impaired endothelium-dependent vasorelaxation in the HF+EECP group compared to the HF control (p<0.05). Endothelium-independent vasorelaxation was not significantly different among the three groups. CONCLUSIONS: Endothelium-dependent vasorelaxation is impaired in the hypercholesterolemic pigs. EECP treatment significantly improves hypercholesterolemia-induced diminished endothelium-dependent vasorelaxation. It suggests that amelioration in endothelial function may at least in part contribute to the beneficial effects of EECP treatment in clinical practice.

Yu H, Zhang W, Yancey PG, Koury MJ, Zhang Y, Fazio S, Linton MF. · Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #16269665 links to  free full text

Abstract: OBJECTIVE: Mice null for both apolipoprotein (apo)E and scavenger receptor (SR)-BI (DKO) develop severe hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarction, and premature death. The current study examines the ability of macrophage apoE to improve the dyslipidemia, reduce atherosclerosis, and rescue the lethal phenotype of DKO mice. METHODS AND RESULTS: Initially, bone marrow transplantation (BMT) was unsuccessful, because the DKO mice died from a rapidly fatal anemia 3 to 5 days after lethal irradiation. Therefore, probucol was used to rescue the DKO mice during BMT and was discontinued 2-weeks after BMT, allowing successful reconstitution with donor marrow. Twelve male apoE(-/-)SR-BI(-/-) mice fed 0.5% probucol in a chow diet were lethally irradiated and transplanted with either wild-type (WT) or DKO bone marrow. Two-weeks after BMT, apoE was detected in serum in WT-->DKO mice, and mean serum cholesterol levels were reduced by 70% versus DKO-->DKO mice. Lipoprotein profiles and HDL subpopulations in WT-->DKO mice were similar to apoE(+/+)SR-BI(-/-)-->DKO mice and resembled those of SR-BI(-/-) mice. In WT-->DKO mice, aortic atherosclerosis was reduced by 88% to 90% versus DKO-->DKO mice. Furthermore, the DKO-->DKO mice died &8 weeks after BMT, whereas WT-->DKO mice exhibited a life span >40 weeks after BMT. CONCLUSIONS: Macrophage apoE is able to rescue the lethal phenotype of apoE(-/-)SR-BI(-/-) mice by improving the dyslipidemia and dramatically reducing atherosclerotic lesion development.

Qin J, Han TQ, Cai XX, Jiang ZH, Yang XM, Zhang Y, Yang SY, Jiang ZY, Zhang SD. · Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai Institute of Digestive Surgery, Shanghai 200025, China. · Zhonghua Liu Xing Bing Xue Za Zhi. · Pubmed #16185464 No free full text.

Abstract: OBJECTIVE: To study the characteristics of inheritance and epidemiology of gallstone disease in one pedigree. METHODS: A gallbladder disease-specific questionnaire was administered to all family members to ascertain histories of cholecystectomy and other medical conditions as well as anthropometrical data. Laboratory examination and ultrasonography were performed to determine the existence of gallstone. RESULTS: One hundred and thirteen members of four generations in the index family were enrolled in the study. The prevalence of gallstone in females (34.48%) was higher than in males (23.64%) but with no significant difference. The prevalence in the second and third generations (52%) was higher than in others (20%) (P < 0.05). The heritability and standard error showed as 86.38% +/- 46.46% in I generations. Body mass index, histories of hypertension, hyperlipidemia and blood glucose were positively related to gallstone disease (P = 0.012, < 0.01, 0.017, 0.043, respectively) in this family. Gallstone disease was not significantly related to history of diabetes, daily alcohol or diet habit. Plasma cholesterol and triglyceride levels were not correlated with gallstone disease. CONCLUSION: Gallstone disease presented aggregation in the family and was in accordance with the characteristics of autosomal dominant inheritance. Being female, obesity, hypertension and history of hyperlipidemia might serve as risk factors to this family.

Shi GQ, Dropinski JF, Zhang Y, Santini C, Sahoo SP, Berger JP, Macnaul KL, Zhou G, Agrawal A, Alvaro R, Cai TQ, Hernandez M, Wright SD, Moller DE, Heck JV, Meinke PT. · Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. · J Med Chem. · Pubmed #16107159 No free full text.

Abstract: The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2-carboxylic acids as highly potent and subtype-selective PPARalpha agonists are reported. Systematic study of structure-activity relationships has identified several key structural elements within this class for maintaining the potency and subtype selectivity. Select compounds were evaluated in animal models of dyslipidemia using Syrian hamsters and male Beagle dogs, and all these compounds displayed excellent cholesterol- and triglyceride-lowering activity at dose levels that were much lower than the marketed weak PPARalpha agonist fenofibrate.