Hyperlipidemias: Zhou L

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.

Zhou L, Wan WJ, Liu LG, Li X, Zhang HX, Zhang TF. · Section of Acupuncture and Moxibustion, Wuhan Hospital of Integrating Chinese Medicine and Western Medicine, Hubei 430022, China. · Zhongguo Zhen Jiu. · Pubmed #18257192 No free full text.

Abstract: OBJECTIVE: To probe the regulative effect of electroacupuncture (EA) at "Fenglong" (ST 40) on blood lipids in hyperlipidemia (HLP) rats and the mechanism. METHODS: Eighty Wistar rats were randomly divided into a normal group (fed with basal forage), a model group (fed with high fat forage), an EA group (fed with high fat forage + EA treatment), a western medicine group (fed with high fat forage + Pravastatin sodium). Contents of serum total cholesterol (TC), triacylglycerol (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), endothelin (ET), nitric oxide (NO) and calcitonin gene-related peptide (CGRP) were determined before and after treatment. RESULTS: Compared with the normal group, the body weight, levels of TC, TG, LDL-C and ET were significantly elevated (P < 0.05, P < 0.01) and the levels of HDL-C, NO and CGRP were significantly decreased (P < 0.05) in the model group; compared with the model group, the body weight, levels of TC, TG and LDL-C were significantly decreased (P < 0.01) and the levels of NO and CGRP were significantly increased in the western medicine group and the EA group (P < 0.01, P < 0.05); compared with the EA group, HDL-C level significantly increased in the western medicine group (P < 0.01), and ET level decreased in the EA group and the western medicine group with no significant difference between the two groups (P > 0.05). CONCLUSION: Both EA and Pravastatin sodium have better benign regulative effects on TC, TG, LDL-C, NO and CGRP and can decrease ET level to a certain extent in the rat of hyperlipidemia.

Chen X, Osborne MC, Rybczynski PJ, Zeck R, Yang M, Xu J, Zhou L, Cryan E, Tang Y, Demarest KT. · Endocrine Therapeutics and Metabolic Disorders Team, Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ 08669, USA. · Diabetes Obes Metab. · Pubmed #16050946 No free full text.

Abstract: AIM: The purpose of this study was to characterize a novel, non-thiazolidinedione (TZD) peroxisome proliferator-activated receptor (PPAR)gamma agonist, RWJ-348260, via both in vitro and in vivo approaches. METHODS: The in vitro PPARgamma activities of RWJ-348260 were assessed in PPARgamma-GAL4 co-transfection assay, PPARgamma receptor binding assay, aP2 gene induction assay and preadipocyte differentiation assay. The in vivo efficacy of the compound was determined in rodent genetic diabetes models [ob/ob mouse, db/db mouse and Zucker diabetic fatty (ZDF) rat] following multiple days of oral administration. RESULTS: RWJ-348260 selectively activated PPARgammain vitro. In vivo, RWJ-348260 produced significant decreases in plasma glucose, HbA1c, insulin and triglyceride levels. RWJ-348260 also dose-dependently improved oral glucose tolerance. In db/db mice, the compound up-regulated PPARgamma target genes in white adipose tissues. RWJ-348260 produced a lower extent of hepatocyte lipid deposition and a smaller increase in liver weight compared to rosiglitazone in db/db mice. While RWJ-348260 effectively normalized hyperglycaemia and dyslipidaemia, it did not change haematocrit, transaminase, alkaline phosphatase, total bilirubin levels or liver weights in ZDF rats. CONCLUSIONS: RWJ-348260 is a potent PPARgamma agonist with efficacious antidiabetic activity in diabetic animal models. The compound has an improved side-effect profile compared to rosiglitazone.

Wu D, Yang H, Xiang W, Zhou L, Shi M, Julies G, Laplante JM, Ballard BR, Guo Z. · Department of Pathology, Anatomy, and Cell Biology, Meharry Medical College, Nashville, TN 37208, USA. · J Lipid Res. · Pubmed #15863839 links to  free full text

Abstract: Individuals with a heterozygous mutation at the ataxia-telangiectasia mutated gene (ATM) have been reported to be predisposed to ischemic heart disease. This report examined for the first time the effect of a heterozygous ATM mutation (ATM(+)(/-)) on plasma lipid levels and atherosclerosis intensity using ATM(+/-), ATM(+)(/+) (wild type), ATM(+)(/+)/LDLR(-)(/-) (low density lipoprotein receptor knockout), ATM(+)(/-)/LDLR(-)(/-), ATM(+)(/+)/ApoE(-)(/-) (apolipoprotein E knockout), and ATM(+)(/-)/ApoE(-)(/-) mice. Our data demonstrated that the plasma cholesterol and triglyceride levels in ATM(+)(/-) and ATM(+)(/-)/LDLR(-)(/-) mice were approximately the same as those in ATM(+)(/+) and ATM(+)(/+)/LDLR(-)(/-) control mice, respectively. In contrast, the plasma cholesterol level was significantly higher in ATM(+)(/-)/ApoE(-)(/-) mice than in ATM(+)(/+)/ApoE(-)(/-) control mice. In addition, the ATM(+)(/-)/ApoE(-)(/-) mice showed higher plasma apoB-48 levels, slower clearance for plasma apoB-48-carrying lipoproteins, and more advanced atherosclerotic lesions in the aorta compared with the ATM(+)(/+)/ApoE(-)(/-) mice. These novel results suggest that the product of ATM is involved in an apoE-independent pathway for catabolism of apoB-48-carrying remnants; therefore, superimposition of a heterozygous ATM mutation onto an ApoE deficiency background reduces the clearance of apoB-48-carrying lipoproteins from the blood circulation and promotes the formation of atherosclerosis.

Zhou L, Dong J, Yu M, Yin H, She M. · Department of Pathology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China. · Exp Gerontol. · Pubmed #14580869 No free full text.

Abstract: The objective of this study was to determine whether there was an age-dependent difference in promoting nuclear translocation of NF-kappa B and platelet derived growth factor expression in aortic endothelial cells between two groups of Wistar rats of 2 and 10 months in age, respectively, accompanied by hypercholesterolemia. The serum cholesterol levels became significantly higher in the older rats after taking a cholesterol-enriched diet for 16 weeks (129.3+/-11.9 vs. 194.5+/-22.6 mg/dl, P<0.01). The increase in total cholesterol levels were due to an elevation of LDL cholesterol since serum HDL cholesterol concentrations were similar in rats on either a high cholesterol- or a standard diet. Immunohistologic staining revealed nuclear translocation of NF-kappaB in aortic endothelial cells of rats was responsible for a high cholesterol uptake by cells. PDGF-B production was also increased in the endothelial cells of these animals as identified by situ hybridization and immunohistologic staining. Interestingly, the intensity of PDGF-B expression in the 10 months old rats was markedly higher than those of 2 months old. Taken together, these findings provide evidence that there was an elevation of serum cholesterol levels coinciding with an increase of PDGF-B expression in older rats, in which NF-kappaB might be an important transcription factor in mediating a hypercholesterolemia-induced PDGF-B expression.

Zhou L, Dong JH, Yu M, Yin HC, She MP. · Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basie Medicine, Peking Union Medical College, Beijing 100005, China. · Zhonghua Bing Li Xue Za Zhi. · Pubmed #14514383 No free full text.

Abstract: OBJECTIVE: To detect whether the activation of nuclear factor-kappa B (NF-kappaB) in endothelial cells induced by mm-LDL can promote platelet-derived growth factor-B (PDGF-B) expression in vitro, and whether it is also present in hypercholesterolemic rats in vivo, influence of age on NF-kappaB and PDGF-B signal transduction pathway. METHODS: Established hypercholesterolemic rat model by feeding with a high-cholesterol ration. The activation of NF-kappaB in aortic endothelial cells was identified by immunohistochemical staining, the expression of PDGF-B mRNA and PDGF-B protein were examined using in situ hybridization and immunohistochemistry respectively. RESULTS: In comparison with the control rats, a positive immunostaining of NF-kappaB in nuclei of aortic endothelial cells of the experimental rats was detected after a high cholesterol ration for 6 weeks. The number of endothelial cells expressing PDGF-B mRNA increased and the intensity was dependent upon the duration of high-cholesterol intake. NF-kappaB translocation (0.461 +/- 0.075 vs. 0.350 +/- 0.094, P < 0.05) and PDGF-B expression in 10-month old Wistar rats were more remarkable than that of 2-month old rats after having cholesterol for 16 weeks. Immunohistochemical staining for PDGF-B gave a similar result (0.230 +/- 0.040 vs. 0.185 +/- 0.037, P < 0.001). CONCLUSIONS: Hypercholesterolemia is capable of activating nuclear translocation of NF-kappaB and promoting expression of PDGF-B in rat aortic endothelial cells in vivo, this coincided with the results obtained in ox-LDL or mm-LDL experiments on endothelial cells in vitro. This phenomenon is much more evident in 10-month old rats which indicates that age might have a close relationship with NF-kappaB - PDGF-B signal transduction pathway.