Hyperlipidemias: Lin M

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.

Lin M, Superko R, Williams P, Lim P, Pan J, Charles MA. · Diabetes Research Center, 2492 Walnut Ave., Suite 130, Tustin, CA 92780, USA. · Diabetes Nutr Metab. · Pubmed #12848306 No free full text.

Abstract: BACKGROUND: Since diabetes is strongly linked to cardiovascular disease, we tested whether: 1) diabetic patients have a high prevalence of the atherogenic lipid profile and 2) the drugs used to treat hyperglycemia are related to the atherogenic lipid profile. METHODS: Seventy-two diabetic patients were retrospectively studied for lipids using the Lipid Research Clinic methods and LDL and HDL gel electrophoreses. RESULTS: Despite normal mean levels of total LDL- and HDL-cholesterol (HDL-c), diabetic patients had abnormal mean levels and an unusually high prevalence of lipid abnormalities not apparent on routine lipid blood tests. Thus, mean LDL peak particle diameter (PPD) was 258 +/- 11A and values < 263A occurred in 57% of diabetic patients; HDL2 < 40% in 61% and Lp(a) > 25 mg/dl occurred in 36% of patients, despite good glycemic control. Mean HbA1c [Diabetes Control and Complications Trial (DCCT) formatted] was 6.5 +/- 1.4%. In contrast to patients using sulfonylureas or metformin, diabetic patients using insulin had significantly larger mean LDL PPD (261 vs 254A, p < 0.006), lower triglycerides (115 vs 215 mg/dl,p < 0.0001), higher HDL-c (53 vs 40 mg/dl,p < 0.0001) and higher HDL2 levels (43 vs 29%, p < 0.0001). CONCLUSIONS: In this diabetic group, traditional guidelines fail to identify patients with high dyslipidemic prevalence rates (84%). Further, certain oral hypoglycemic treatments are associated with less favorable atherogenic lipid profiles when compared to insulin treatment.

Jiang XC, Tall AR, Qin S, Lin M, Schneider M, Lalanne F, Deckert V, Desrumaux C, Athias A, Witztum JL, Lagrost L. · Downstate Medical Center, State University of New York, New York, New York 11203, USA. · J Biol Chem. · Pubmed #12105225 links to  free full text

Abstract: Vitamin E is a lipophilic anti-oxidant that can prevent the oxidative damage of atherogenic lipoproteins. However, human trials with vitamin E have been disappointing, perhaps related to ineffective levels of vitamin E in atherogenic apoB-containing lipoproteins. Phospholipid transfer protein (PLTP) promotes vitamin E removal from atherogenic lipoproteins in vitro, and PLTP deficiency has recently been recognized as an anti-atherogenic state. To determine whether PLTP regulates lipoprotein vitamin E content in vivo, we measured alpha-tocopherol content and oxidation parameters of lipoproteins from PLTP-deficient mice in wild type, apoE-deficient, low density lipoprotein (LDL) receptor-deficient, or apoB/cholesteryl ester transfer protein transgenic backgrounds. In all four backgrounds, the vitamin E content of very low density lipoprotein (VLDL) and/or LDL was significantly increased in PLTP-deficient mice, compared with controls with normal plasma PLTP activity. Moreover, PLTP deficiency produced a dramatic delay in generation of conjugated dienes in oxidized apoB-containing lipoproteins as well as markedly lower titers of plasma IgG autoantibodies to oxidized LDL. The addition of purified PLTP to deficient plasma lowered the vitamin E content of VLDL plus LDL and normalized the generation of conjugated dienes. The data show that PLTP regulates the bioavailability of vitamin E in atherogenic lipoproteins and suggest a novel strategy for achieving more effective concentrations of anti-oxidants in lipoproteins, independent of dietary supplementation.