Plasma Lipases And Lipid Transfer Proteins Increase Phospholipid But Not Free Cholesterol Transfer From Lipid Emulsion To High Density Lipoproteins

Background: Plasma lipases and lipid transfer proteins are involved in the generation and speciation of high density lipoproteins. In this study we have examined the influence of plasma lipases and lipid transfer protein activities on the transfer of free cholesterol (FC) and phospholipids (PL) from lipid emulsion to human, rat and mouse lipoproteins. The effect of the lipases was verified by incubation of labeled (3H-FC, 14C-PL) triglyceride rich emulsion with human plasma (control, post-heparin and post-heparin plus lipase inhibitor), rat plasma (control and post-heparin) and by the injection of the labeled lipid emulsion into control and heparinized functionally hepatectomized rats. Results: In vitro, the lipase enriched plasma stimulated significantly the transfer of 14C-PL from emulsion to high density lipoprotein (p<0.001) but did not modify the transfer of 3H-FC. In hepatectomized rats, heparin stimulation of intravascular lipolysis increased the plasma removal of 14C-PL and the amount of 14C-PL found in the low density lipoprotein density fraction but not in the high density lipoprotein density fraction. The in vitro and in vivo experiments showed that free cholesterol and phospholipids were transferred from lipid emulsion to plasma lipoproteins independently from each other. The incubation of human plasma, control and control plus monoclonal antibody anti-cholesteryl ester transfer protein (CETP), with 14C-PL emulsion showed that CETP increases 14C-PL transfer to human HDL, since its partial inhibition by the anti-CETP antibody reduced significantly the 14C-PL transfer (p<0.05). However, comparing the nontransgenic (no CETP activity) with the CETP transgenic mouse plasma, no effect of CETP on the 14C-PL distribution in mice lipoproteins was observed. Conclusions: It is concluded that: 1-intravascular lipases stimulate phospholipid transfer protein mediated phospholipid transfer, but not free cholesterol, from triglyceride rich particles to human high density lipoproteins and rat low density lipoproteins and high density lipoproteins; 2-free cholesterol and phospholipids are transferred from triglyceride rich particles to plasma lipoproteins by distinct mechanisms, and 3 - CETP also contributes to phospholipid transfer activity in human plasma but not in transgenic mice plasma, a species which has high levels of the specific phospholipid transfer protein activity.219Backer, G., Bacquer, D., Konitzer, M., Epidemiological aspects of high density lipoprotein cholesterol (1998) Atherosclerosis, 137, pp. S1-S6Stein, O., Stein, Y., Atheroprotective mechanisms of HDL (1999) Atherosclerosis, 144, pp. 285-301Tall, A.R., Plasma lipid transfer proteins (1995) Annu Rev Biochem, 64, pp. 235-257Hesler, B., Tall, A.R., Swenson, T.L., Weech, P.K., Marcel, Y.L., Milne, R.W., Monoclonal antibody to the Mr 74000 cholesterol ester transfer protein neutralize all of the cholesterol ester and triglyceride transfer activities in human plasma (1988) J Biol Chem, 263, pp. 5020-5023Swenson, T.L., Brocia, R.W., Tall, A.R., Plasma cholesteryl ester transfer protein has binding sites for neutral lipids and phospholipids (1988) J Biol Chem, 263, pp. 5150-5157Lagrost, L., Athias, A., Gambert, P., Lallemant, C., Comparative study of phospholipid transfer activities mediated by cholesteryl ester transfer protein and phospholipid transfer protein (1994) J Lipid Res, 35, pp. 825-835Tato, F., Vega, G.L., Grundy, S.M., Determinants of plasma HDL-cholesterol in hypertriglyceridemic patients (1997) Arterioscler Thromb Vasc Biol, 17, pp. 56-63Tall, A.R., Forester, L.R., Bongiovanni, G.L., Facilitation of phosphatidylcholine transfer into HDL lipoproteins by an apolipoprotein in the density 1.20-1.26 g/ml fraction of plasma (1983) J Lipid Res, 24, pp. 277-289Albers, J.J., Tollefson, J.H., Chen, C.H., Steinmetz, A., Isolation and characterization of human plasma lipid transfer proteins (1984) Arteriosclerosis, 4, pp. 49-58Guyard-Dangremont, V., Desrumaux, C., Gambert, P., Lallemant, C., Lagrost, L., Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. 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Does Plasma Hdl-c Concentration Interact With Whole-body Cholesterol Metabolism?

This review examines the interactions between plasma high density lipoprotein (HDL) metabolism and whole-body cholesterol economy. More specifically, this review addresses three questions: 1) does plasma HDL-C concentration correlate with the parameters of whole-body cholesterol metabolism? 2) Do variations in cholesterol metabolism interfere with plasma HDL-C concentrations? 3) Are the markers of cholesterol synthesis and intestinal absorption specifically under the control of plasma HDL? The following answers were provided to each question, respectively: 1) plasma HDL influences whole-body cholesterol synthesis rate but the evidence that HDL modifies the total amount of cholesterol absorbed by the intestine is not clearly supported by present investigations; 2) there are suggestions that changes in whole body cholesterol metabolism rates do not interfere with plasma HDL-C concentrations; 3) markers of cholesterol synthesis and absorption may specifically be controlled by plasma HDL-C concentrations regarding the genetic causes of extremely low HDL-C concentrations, although within the general population plasma HDL-C concentration is likely ascribed to insulin resistance or diabetes mellitus. © 2012 Elsevier B.V.234279284Briel, M., Ferreira-Gonzalez, I., You, J.J., Karanicolas, P.J., Akl, E.A., Wu, P., Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis (2009) BMJ, 338, pp. b92Rea, T.J., Brown, C.M., Sing, C.F., Complex adaptive system models and the genetic analysis of plasma HDL-cholesterol concentration (2006) Perspect Biol Med, 49, pp. 490-503Barter, P., Kastelein, J., Nunn, A., High density lipoproteins (HDLs) and atherosclerosisthe unanswered questions (2003) Atherosclerosis, 168, pp. 195-211. , Hobbs, Future Forum Editorial BoardRashid, S., Watanabe, T., Sakaue, T., Lewis, G.F., Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity (2003) Clin Biochem, 36, pp. 421-429Kontush, A., Chapman, M.J., Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis (2006) Pharmacol Rev, 58, pp. 342-374Miettinen, T.A., Tilvis, R.S., Kesäniemi, Y.A., Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population (1990) Am J Epidemiol, 131, pp. 20-31Kempen, H.J., Glatz, J.F., Gevers Leuven, J.A., van der Voort, H.A., Katan, M.B., Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans (1988) J Lipid Res, 29, pp. 1149-1155Vanhanen, H., Kesäniemi, Y.A., Miettinen, T.A., Pravastatin lowers serum cholesterol, cholesterol-precursor sterols, fecal steroids, and cholesterol absorption in man (1992) Metabolism, 41, pp. 588-595Simonen, P., Gylling, H., Howard, A.N., Miettinen, T.A., Introducing a new component of the metabolic syndrome: low cholesterol absorption (2000) Am J Clin Nutr, 72, pp. 82-88Santosa, S., Varady, K.A., AbuMweis, S., Jones, P.J., Physiological and therapeutic factors affecting cholesterol metabolism: does a reciprocal relationship between cholesterol absorption and synthesis really exist? 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Increased 27-hydroxycholesterol Plasma Level In Men With Low High Density Lipoprotein-cholesterol May Circumvent Their Reduced Cell Cholesterol Efflux Rate

Background: HDL is considered the most important mechanism for the excretion of intracellular cholesterol. The liver is the only organ capable to metabolize cholesterol into bile acid. The enzymatic conversion of cholesterol to bile acid is dependent on the cytochrome P450 microsomal system which is also responsible for the generation of oxysterols. The latter's plasma concentrations may reflect the metabolic processes of specific tissues where they are generated. The objective of this study was to investigate in healthy individuals who differ according to their HDL levels the concentration of oxysterols and relate it to the HDL-dependent cell cholesterol efflux rate. Methods: 24-Hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol were determined in plasma by GLC/mass spectrometry in 107 healthy subjects with low HDL (HDL-C. . 1.55. mmol/l). HDL-dependent in vitro cell cholesterol efflux rate was measured in 29 cases. Results: No differences were found in plasma oxysterol concentrations between the Low HDL and High HDL groups. There was a significant negative correlation between HDL-C and 27-hydroxycholesterol. Plasma oxysterol concentrations were significantly lower in female than in male subjects. The Low HDL male group had higher 27-hydroxycholesterol than the High HDL male group. Cell cholesterol efflux rate was lower in Low HDL than in High HDL and related inversely with 27-hydroxycholesterol. Conclusion: As compared to High HDL, Low HDL men have increased 27-hydroxycholesterol plasma level that may circumvent their reduced cell cholesterol efflux rate. © 2014 Elsevier B.V.433169173Gordon, T., Castelli, W.P., Hjortland, M.C., Kannel, W.B., Dawber, T.R., High density lipoprotein as a protective factor against coronary heart disease. 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Reference Values For High-density Lipoprotein Particle Size And Volume By Dynamic Light Scattering In A Brazilian Population Sample And Their Relationships With Metabolic Parameters

Background: Current data indicate that the size of high-density lipoprotein (HDL) may be considered an important marker for cardiovascular disease risk. We established reference values of mean HDL size and volume in an asymptomatic representative Brazilian population sample (n= 590) and their associations with metabolic parameters by gender. Methods: Size and volume were determined in HDL isolated from plasma by polyethyleneglycol precipitation of apoB-containing lipoproteins and measured using the dynamic light scattering (DLS) technique. Results: Although the gender and age distributions agreed with other studies, the mean HDL size reference value was slightly lower than in some other populations. Both HDL size and volume were influenced by gender and varied according to age. HDL size was associated with age and HDL-C (total population); non- white ethnicity and CETP inversely (females); HDL-C and PLTP mass (males). On the other hand, HDL volume was determined only by HDL-C (total population and in both genders) and by PLTP mass (males). Conclusions: The reference values for mean HDL size and volume using the DLS technique were established in an asymptomatic and representative Brazilian population sample, as well as their related metabolic factors. 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Effects Of Atorvastatin And T-786c Polymorphism Of Enos Gene On Plasma Metabolic Lipid Parameters

Background: Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. Objective: This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). Methods: Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. Results: The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p ≤ 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p ≤ 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p ≤ 0.07) and lipoprotein (a) (Lp(a)) (p ≤ 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. Conclusion: These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.10011420Hadi, H.A., Suwaidi, J.A., Endothelial dysfunction in diabetes mellitus (2007) Vasc Health Risk Manag, 3 (6), pp. 853-876Higashi, Y., Noma, K., Yoshizumi, M., Kihara, Y., Endothelial function and oxidative stress in cardiovascular diseases (2009) Circ J, 73 (3), pp. 411-418Alderton, W.K., Cooper, C.E., Knowles, R.G., Nitric oxide synthases: Structure, function and inhibition (2001) Biochem J, 357 (3 PT.), pp. 593-615Cunningham, K.S., Gotlieb, A.I., The role of shear stress in the pathogenesis of atherosclerosis (2005) Lab Invest, 85 (1), pp. 9-23Napoli, C., Ignarro, L.J., Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases (2009) Arch Pharm Res, 32 (8), pp. 1103-1108Tai, S.C., Robb, G.B., Marsden, P.A., Endothelial nitric oxide synthase: 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cardiovascular mortality with the prophylactic use of statins (2010) Basic Clin Pharmacol Toxicol, 106 (5), pp. 357-361Fatini, C., Sofi, F., Sticchi, E., Gensini, F., Gori, A.M., Fedi, S., Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes (2004) Am Heart J, 147 (3), pp. 516-521Alvarez, R., Gonzalez, P., Batalla, A., Reguero, J.R., Iglesias-Cubero, G., Hevia, S., Association between the NOS3 (-786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease (2001) Nitric Oxide, 5 (4), pp. 343-348Igarashi, J., Miyoshi, M., Hashimoto, T., Kubota, Y., Kosaka, H., Statins induce S1P1 receptors and enhance endothelial nitric oxide production in response to high-density lipoproteins (2007) Br J Pharmacol, 150 (4), pp. 470-479Blum, A., Shamburek, R., The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis 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