| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Endoscopic sinus surgery in cases of cholesterol granuloma of the maxillary sinus Kikuchi, T., E. So, et al. (2002), Tohoku J Exp Med 197(4): 233-7. Abstract: Cholesterol granuloma is usually associated with middle ear disease and is very rare in the paranasal sinuses. We report a case of cholesterol granuloma originating in the maxillary sinus of a 52-year-old female. Endoscopic sinus surgery was performed on the left maxillary sinus, and the cholesterol granuloma was successfully removed by the middle meatal antrostomy. Light microscopic examination showed granulomatous tissue with typical cholesterol clefts, multinucleated foreign body giant cells, small areas of hemorrhage, hemosiderin-laden macrophages and plasma cells. We also describe the details of the endoscopic surgical techniques employed in the treatment of this disorder. |
| Endoscopic treatment of maxillary sinus cholesterol granuloma Marks, S. C. and D. M. Smith (1995), Laryngoscope 105(5 Pt 1): 551-2. |
| Endosome to Golgi transport of ricin is regulated by cholesterol Grimmer, S., T. G. Iversen, et al. (2000), Mol Biol Cell 11(12): 4205-16. Abstract: We have here studied the role of cholesterol in transport of ricin from endosomes to the Golgi apparatus. Ricin is endocytosed even when cells are depleted for cholesterol by using methyl-beta-cyclodextrin (m beta CD). However, as here shown, the intracellular transport of ricin from endosomes to the Golgi apparatus, measured by quantifying sulfation of a modified ricin molecule, is strongly inhibited when the cholesterol content of the cell is reduced. On the other hand, increasing the level of cholesterol by treating cells with mbetaCD saturated with cholesterol (m beta CD/chol) reduced the intracellular transport of ricin to the Golgi apparatus even more strongly. The intracellular transport routes affected include both Rab9-independent and Rab9-dependent pathways to the Golgi apparatus, since both sulfation of ricin after induced expression of mutant Rab9 (mRab9) to inhibit late endosome to Golgi transport and sulfation of a modified mannose 6-phosphate receptor (M6PR) were inhibited after removal or addition of cholesterol. Furthermore, the structure of the Golgi apparatus was affected by increased levels of cholesterol, as visualized by pronounced vesiculation and formation of smaller stacks. Thus, our results indicate that transport of ricin from endosomes to the Golgi apparatus is influenced by the cholesterol content of the cell. |
| Endothelial and neuronal functions in cerebral and temporal arteries from monkeys fed a high-cholesterol diet Ayajiki, K., H. Fujioka, et al. (2002), J Cardiovasc Pharmacol 40(3): 456-66. Abstract: Modifications by hyperlipidemia of endothelium-dependent and -independent relaxations were evaluated in cerebral and temporal arteries from control and hyperlipidemic (high cholesterol-fed) monkeys. Histologically atherosclerotic lesions were not observed in either group. Relaxations induced by histamine, abolished by N(G)-nitro->L-arginine (>L-NA), were significantly potentiated in the hyperlipidemic monkey cerebral arteries, compared with those in the arteries from control monkeys. Treatment with superoxide dismutase did not affect the histamine-induced relaxation. Conversely, endothelium-dependent relaxations induced by A23187, Ca2+ ionophore, in cerebral arteries did not differ between control and hyperlipidemic monkeys. In temporal arteries, relaxations by acetylcholine and A23187 did not differ between control and hyperlipidemic monkeys. Endothelium-dependent and -independent relaxations by adenosine diphosphate in cerebral and temporal arteries were not affected by hyperlipidemia. Endothelium-independent relaxations by exogenously applied nitric oxide did not differ in the arteries from control and hyperlipidemic monkeys. Nicotine-induced relaxations in cerebral arteries, which were mediated with nitric oxide released from nitroxidergic (nitrergic) nerves, and the contractions caused by nicotine in temporal and mesenteric arteries treated with >L-NA did not differ between control and hyperlipidemic monkeys. It is concluded that long exposure to hyperlipidemia did not affect endothelial functions of monkey middle cerebral and temporal arteries but enhanced nitric oxide-mediated relaxations caused by histamine, possibly due to upregulation of endothelial histamine receptor-mediated functions in the cerebral arteries. The nitroxidergic (nitrergic) and adrenergic nerve functions do not seem to be affected by hyperlipidemia. |
| Endothelial cell morphometry of atherosclerotic lesions and flow profiles at aortic bifurcations in cholesterol fed rabbits Okano, M. and Y. Yoshida (1992), J Biomech Eng 114(3): 301-8. Abstract: Observations on shapes of endothelial cells both in sudanophilic and nonsudanophilic regions at bifurcations of the brachiocephalic (BC) and left subclavian (SA) arteries in hyperlipidemic rabbits were performed under a SEM. The stagnation point of flow and leading edges of flow dividers were nonsudanophilic and covered by round and long fusiform endothelial cells, respectively. The hips of flow dividers of both branchings, proven to be relatively low shear stress regions, by movement of microspheres in steady flow, were sudanophilic and covered by ellipsoidal cells. Similar studies were carried out in normolipidemic rabbits. It might be concluded that lipid deposition in hyperlipidemic rabbits occurs in relatively low shear stress regions, where endothelial cells are functionally activated, rather than in laminar high shear stress regions at the flow divider. |
| Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity Strauss, J. G., R. Zimmermann, et al. (2002), Biochem J 368(Pt 1): 69-79. Abstract: Endothelial cell-derived lipase (EDL) is a new member of the lipase gene family with high sequence homology with lipoprotein lipase (LPL). EDL is a phospholipase with very little triacylglycerol lipase activity. To investigate the effects of EDL on binding and uptake of high-density lipoprotein (HDL), as well as on the selective uptake of HDL-derived cholesterol esters (CEs), HepG2 cells were infected with adenovirus coding for EDL. For comparison, cells were also infected with LPL and with lacZ as a control. Both HDL binding and particle uptake were increased 1.5-fold and selective HDL-CE uptake was increased 1.8-fold in EDL-infected HepG2 cells compared with controls. The effect of LPL was less pronounced, resulting in 1.1-fold increase in particle uptake and 1.3-fold increase in selective uptake. Inhibition of the enzymic activity with tetrahydrolipstatin (THL) significantly enhanced the effect of EDL, as reflected by a 5.2-fold increase in binding, a 2.6-fold increase in particle uptake and a 1.1-fold increase in CE selective uptake compared with incubations without THL. To elucidate the mechanism responsible for the effects of THL, we analysed the abundance of heparin-releasable EDL protein from infected HepG2 cells upon incubations with THL, HDL and free (non-esterified) fatty acids (FFAs). In the presence of THL, vastly more EDL protein remained bound to the cell surface. Additionally, HDL and FFAs reduced the amount of cell-surface-bound EDL, suggesting that fatty acids that are liberated from phospholipids in HDL release EDL from the cell surface. This was substantiated further by the finding that, in contrast with EDL, the amount of cell-surface-bound enzymically inactive mutant EDL (MUT-EDL) was not reduced in the presence of HDL and foetal calf serum. The increased amount of cell-surface-bound MUT-EDL in the presence of THL suggested that the enzymic inactivity of MUT-EDL, as well as an augmenting effect of THL that is independent of its ability to inactivate the enzyme, are responsible for the increased amount of cell-surface-bound EDL in the presence of THL. Furthermore, in cells expressing MUT-EDL, binding and holoparticle uptake were markedly higher compared with cells expressing the active EDL, and could be increased further in the presence of THL. Despite 1.7-fold higher binding and 1.8-fold higher holoparticle uptake, the selective CE uptake by MUT-EDL-expressing cells was comparable with EDL-expressing cells and was even decreased 1.3-fold with THL. Experiments in CLA-1 (CD-36 and LIMPII analogous 1, the human homologue of scavenger receptor class B type I)-deficient HEK-293 cells demonstrated that EDL alone has the ability to stimulate HDL-CE selective uptake independently of CLA-1. Thus our results demonstrate that EDL mediates both HDL binding and uptake, and the selective uptake of HDL-CE, independently of lipolysis and CLA-1. |
| Endothelial dysfunction is associated with cholesterol levels in the high normal range in humans Steinberg, H. O., B. Bayazeed, et al. (1997), Circulation 96(10): 3287-93. Abstract: BACKGROUND: The purpose of this study was to test the hypothesis that cholesterol levels in the high normal range are associated with impaired endothelium-dependent vasodilation. METHODS AND RESULTS: We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) in normal volunteers exhibiting a wide range of total cholesterol levels within the normal range (<75th percentile). LBF increased in a dose-dependent fashion in response to the femoral artery infusions of MCh and SNP (P<.001). LBF responses to MCh were significantly blunted (P<.001) in subjects with high normal cholesterol (195+/-6 mg/dL, n=13) compared with subjects with low normal cholesterol (146+/-5 mg/dL, n=20). Maximal endothelium-dependent vasodilation in the high normal group was decreased by nearly 50% compared with the low normal group (146+/-13% versus 268+/-34%, P<.01). There was a negative correlation between total cholesterol levels and maximal endothelium-dependent vasodilation (total cholesterol, r=-.41, P<.02; LDL cholesterol, r=-.42, P<.02). On the other hand, LBF responses to the endothelium-independent vasodilator SNP did not differ between groups. CONCLUSIONS: These data suggest that an inverse and continuous relationship exists between the prevailing cholesterol level and endothelium-dependent vasodilation. Moreover, cholesterol levels even in the normal range may be associated with endothelial dysfunction, thus potentially contributing to the increased risk of macrovascular disease conferred by cholesterol elevations. |
| Endothelial function in coronary arterioles from pigs with early-stage coronary disease induced by high-fat, high-cholesterol diet: effect of exercise Henderson, K. K., J. R. Turk, et al. (2004), J Appl Physiol 97(3): 1159-68. Abstract: Because hypercholesterolemia can attenuate endothelial function and exercise training can augment endothelial function, we hypothesized that exercise training would improve endothelial function of coronary arterioles from pigs in the early stages of cardiovascular disease induced by a high-fat, high-cholesterol (HF) diet. Yucatan miniature swine were fed a normal-fat (NF) diet or HF diet (2% cholesterol) for 20 wk in which 8 and 46% of their calories were derived from fat, respectively. Both groups were subdivided into sedentary (Sed) or exercise-trained (Ex) groups. This resulted in four experimental groups: NFSed, NFEx, HFSed, and HFEx. Endothelial function was assessed in coronary arterioles 75-100 microm in diameter dissected from the left ventricular apex. Responses to endothelial-dependent dilation induced by bradykinin (BK), ADP, and flow were similar in all four groups, whereas dilation to aggregating platelets in the presence of indomethacin and ketanserin was attenuated in HFSed arterioles (P = 0.01). The attenuated response to aggregating platelets was prevented or reversed in HFEx arterioles (P = 0.03). In HFSed arterioles, BK induced release of an indomethacin-sensitive prostanoid constrictor. In contrast, after exercise training, there was no evidence of this constrictor and BK-induced release of an indomethacin-sensitive prostanoid dilator in HFEx arterioles (P = 0.04). Endothelial nitric oxide synthase protein in arterioles was significantly reduced in HF groups (P < 0.05) and increased in Ex groups (P < 0.05). Interestingly, the relative contribution of nitric oxide to BK-induced dilation, as assessed with nitro-L-arginine methyl ester, was similar in arterioles in the NF, HF, Sed, and Ex groups. These results suggest that, in the early stages of cardiovascular disease, a high-fat, high-cholesterol diet has modest effects on endothelial-dependent dilation in coronary arterioles; nonetheless, these effects are prevented or reversed with exercise training. |
| Endothelial lipase and cholesterol metabolism Cilingiroglu, M. and C. Ballantyne (2004), Curr Atheroscler Rep 6(2): 126-30. Abstract: Endothelial lipase (EL), a new member of the lipase gene family, was recently cloned and has a significant role in plasma high-density lipoprotein levels (HDL). EL has a highly similar molecular homology to lipoprotein lipase and hepatic lipase. It is synthesized by endothelial cells and functions at the cell surface. EL primarily has phospholipase A1 activity. Animals that overexpress EL showed decreased HDL cholesterol levels and those that lack EL show elevated levels of HDL cholesterol. The expression is highly regulated by cytokines and physical forces. These data suggest that EL may play a significant role in atherosclerosis. |
| Endothelial lipase-modified high-density lipoprotein exhibits diminished ability to mediate SR-BI (scavenger receptor B type I)-dependent free-cholesterol efflux Gauster, M., O. V. Oskolkova, et al. (2004), Biochem J 382(Pt 1): 75-82. Abstract: Endothelial lipase (EL) is a phospholipase with little triacylglycerol lipase activity. To assess structural and functional properties of EL-HDL (EL-modified high-density lipoprotein), HDL was incubated with conditioned medium from Cos-7 cells infected with adenovirus encoding human EL. After re-isolation of HDL by ultracentrifugation, TLC and HPLC analyses revealed that EL-HDL was markedly depleted in phosphatidylcholine and enriched in lyso-phosphatidylcholine compared with LacZ-HDL (control HDL) incubated with conditioned medium from Cos-7 cells infected with adenovirus encoding beta-galactosidase. The EL-HDL was enriched in non-esterified fatty acids and, as revealed by lipid electrophoresis, was more negatively charged than control HDL. The HDL particle size as well as the total cholesterol, free cholesterol and triacylglycerol content of HDL were not significantly altered after EL modification. The ability of EL-HDL to mediate 3H-cholesterol efflux from SR-BI (scavenger receptor B type I) overexpressing Chinese-hamster ovary cells was impaired and markedly lower compared with LacZ-HDL at HDL concentrations of 100 microg/ml and above. Studies with 125I-labelled HDL showed almost unaltered binding affinity (K(m) values) and a slightly but significantly decreased binding capacity (B(max) values) of EL-HDL to SR-BI, compared with LacZ-HDL. The ATP-binding-cassette transporter A1-dependent cholesterol and phospholipid effluxes were not affected by EL modification. From these results, we concluded that EL modification alters chemical composition and physical properties of HDL, resulting in its decreased binding capacity to SR-BI and a diminished ability to mediate SR-BI-dependent cholesterol efflux. |
| Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endothelial function Bilsborough, W., D. J. Green, et al. (2003), Atherosclerosis 169(1): 131-8. Abstract: Nitric oxide-dependent vasodilation is impaired early in the pathogenesis of vascular disease. Both the 4ab polymorphism of endothelial nitric oxide synthase (eNOS) and elevated plasma homocysteine are putatively associated with coronary artery disease (CAD). Few studies have investigated the influence of either on endothelial function in normal subjects. We aimed to examine any effect of three eNOS gene polymorphisms and plasma levels of homocysteine, folate and lipids on vascular endothelial function in normal healthy subjects. Community subjects (n=60) were selected for their eNOS genotype. Largely NOz.-dependent, flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) were measured. Neither FMD nor response to GTN in 4a allele carriers was significantly different from that of 4b homozygotes, (7.1+/-0.5 S.E.M. vs. 7.1+/-0.6%) and (18.9+/-1.2 vs. 18.9+/-0.9%), respectively. Responses were also independent of the other polymorphisms. FMD was significantly correlated with HDL-cholesterol (P=0.02). After accounting for serum folate, there was a significant inverse correlation between FMD and plasma homocysteine (P=0.03). In these normal community subjects, plasma homocysteine and HDL-cholesterol were predictors of FMD despite subjects being recruited without regard to these variables and despite normal plasma levels. |
| Endothelin-1-induced incorporation of cholesterol into rat adrenals Romero, D. G., A. Pecci, et al. (1996), Steroids 61(5): 317-22. Abstract: The effect of endothelin-1 (ET-1) on cholesterol uptake by adrenal cortex was evaluated through several experimental approaches: infusion of ET-1 followed by measurement of endogenous cholesterol in excised adrenals; infusion of ET-1 followed by tritiated cholesterol incorporation into adrenal quarters in vitro; coinfusion of ET-1 with tritiated cholesterol-enriched serum and determination of adrenal-associated radioactivity; and tritiated cholesterol incorporation in incubations of adrenal cells. In all cases ET-1 increased cholesterol uptake. Subcellular fractionation showed an ET-1-mediated augmentation in mitochondrial fraction. This increase was mediated by the subpopulation B of adrenal receptors for ET-1. In addition, ET-1 also increased cytochrome P450-SCC (side-chain cleavage) activity. |
| Endothelin-converting enzyme activity in serum lipoprotein and total cholesterol level Ohwaki, T., Y. Hirata, et al. (1993), Atherosclerosis 102(2): 227-8. |
| Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL cholesterol Lewis, T. V., A. M. Dart, et al. (1999), J Am Coll Cardiol 33(3): 805-12. Abstract: OBJECTIVES: Patients with high triglyceride (of which very low density lipoproteins VLDL are the main carriers), but with normal low density lipoprotein (LDL) cholesterol levels, were examined for in vivo endothelium function status. BACKGROUND: Very low density lipoproteins inhibit endothelium-dependent, but not -independent, vasorelaxation in vitro. METHODS: Three groups were studied: 1) healthy volunteers (n = 10; triglyceride 1.24+/-0.14 mmol/liter, LDL cholesterol 2.99+/-0.24 mmol/liter); 2) hypertriglyceridemic (n = 11; triglyceride 6.97+/-1.19 mmol/liter, LDL cholesterol 2.17+/-0.2 mmol/liter, p < 0.05); and 3) hypercholesterolemic (n = 10; triglyceride 2.25+/-0.29 mmol/liter, LDL cholesterol 5.61+/-0.54 mmol/liter; p < 0.05) patients. Vasoactive responses to acetylcholine, sodium nitroprusside, noradrenaline, N(G)-monomethyl-L-arginine and postischemic hyperemia were determined using forearm venous occlusion plethysmography. RESULTS: Responses to acetylcholine (37 microg/min) were significantly dampened both in hypercholesterolemic (% increase in forearm blood flow: 268.2+/-62) and hypertriglyceridemic patients (232.6+/-45.2) when compared with controls (547.8+/-108.9; ANOVA p < 0.05). Responses to sodium nitroprusside (at 1.6 microg/min: controls vs. hypercholesterolemics vs. hypertriglyceridemic: 168.7+/- 25.1 vs. 140.6+/-38.9 vs. 178.5+/-54.5% increase), noradrenaline, N(G)-monomethyl-L-arginine and postischemic hyperemic responses were not different among the groups examined. CONCLUSIONS: Acetylcholine responses are impaired in patients with pathophysiologic levels of plasma triglycerides but normal plasma levels of LDL cholesterol. The impairment observed was comparable to that obtained in hypercholesterolemic patients. We conclude that impaired responses to acetylcholine normally associated with hypercholesterolemia also occur in hypertriglyceridemia. These findings identify a potential mechanism by which high plasma triglyceride levels may be atherogenic independent of LDL cholesterol levels. |
| Endotoxin, TNF, and IL-1 decrease cholesterol 7 alpha-hydroxylase mRNA levels and activity Feingold, K. R., D. K. Spady, et al. (1996), J Lipid Res 37(2): 223-8. Abstract: Endotoxin (LPS) and cytokines increase cholesterol synthesis and the secretion of lipoproteins by the liver in rodents resulting in hypercholesterolemia. Cholesterol 7 alpha-hydroxylase (CAH) is the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, the major regulated pathway by which cholesterol is eliminated from the body. Decreases in CAH would increase the quantity of cholesterol available for lipoprotein production. In the present study, we demonstrate that LPS, TNF, or IL-1 administration to Syrian hamsters produces a marked decrease in the levels of CAH mRNA in the liver. This marked decrease occurred even when the basal level of CAH expression was increased by feeding the bile acid sequestrant, colestipol. Additionally, a marked decrease was also observed when the animals were fed a cholesterol-enriched diet. Moreover, the decrease in CAH mRNA occurred very rapidly (decreased 66% by 90 min after LPS administration) and required relatively small doses of LPS (100 ng/100 g body weight). Lastly, the decrease in mRNA levels was accompanied by a decrease in CAH activity. This decrease in CAH could contribute to the increase in hepatic lipoprotein production induced by LPS and cytokines. CAH can be added to the growing list of proteins that regulate lipid metabolism and that are altered during the acute phase response. |
| Endpoint colorimetric method for assaying total cholesterol in serum with cholesterol dehydrogenase Kayamori, Y., H. Hatsuyama, et al. (1999), Clin Chem 45(12): 2158-63. Abstract: BACKGROUND: Various methods are available to measure serum cholesterol concentrations. Of these, the cholesterol ester hydrolase (CEH)-cholesterol oxidase-peroxidase chromogenic method is widely used. However, this method has the disadvantage of interference by reducing substances. We developed and evaluated an endpoint assay for serum cholesterol, based on a CEH-cholesterol dehydrogenase (CDH)-ultraviolet method. METHODS: Cholesterol esters are first hydrolyzed to free cholesterol by CEH. The free cholesterol is then reduced by CDH to cholest-4-ene-3-one with the simultaneous production of beta-NADH from beta-NAD(+). At equilibrium, the CDH reaction gives incomplete conversion of cholesterol to cholest-4-ene-3-one. To overcome this disadvantage, we added hydrazine monohydrate to the reaction mixture to remove cholest-4-ene-3-one, which allowed the reaction to proceed to completion and gave stoichiometric production of beta-NADH from the reaction of beta-NAD(+) with cholesterol. RESULTS: We tested whether the amount of cholesterol added was equivalent to the absorbance change of NADH at 340 nm with six aqueous samples. Recoveries were 97.1-100.3%. The reaction was linear up to 20.28 mmol/L. The mean within-day (n = 20) and between-day (n = 10) imprecision (CV) was 0. 29-0.43% and 0.22-0.61%, respectively. No interference by bilirubin, hemoglobin, ascorbic acid, and other reducing agents was observed. The equation obtained in comparison with the modified Abell-Levy-Brodie-Kendall method was: y = 0.992x - 0.0058 mmol/L; r = 0.997; S(y|x) = 0.117 mmol/L; n = 50. CONCLUSION: This method is an accurate, reliable method for serum cholesterol analysis and is amenable to automation. |
| Enhanced amphotericin B nephrotoxicity in intensive care patients with elevated levels of low-density lipoprotein cholesterol Wasan, K. M. and J. S. Conklin (1997), Clin Infect Dis 24(1): 78-80. |
| Enhanced capacities and selectivities for cholesterol in aqueous media by molecular imprinting: role of novel cross-linkers Gore, M. A., R. N. Karmalkar, et al. (2004), J Chromatogr B Analyt Technol Biomed Life Sci 804(1): 211-21. Abstract: Molecularly imprinted polymers are being increasingly investigated as selective sorbents. For the recovery of cholesterol from aqueous media, the utility of the molecularly imprinted polymers has been limited by modest capacities and selectivities, especially when compared with alternative adsorbents reported for the binding of bile acids Macromolecules 34 (2001) 1548. This paper describes the use of cholesterol conjugated monomers and cross-linkers, which bind to the template cholesterol molecule by hydrophobic interactions. This leads to enhanced capacities and selectivities during the recovery of cholesterol from aqueous media. The templating effect is clearly seen in the enhanced capacity and selectivity in the retention of cholesterol vis-a-vis stigmasterol and testosterone. |
| Enhanced cholesterol efflux by tyrosyl radical-oxidized high density lipoprotein is mediated by apolipoprotein AI-AII heterodimers Wang, W. Q., D. L. Merriam, et al. (1998), J Biol Chem 273(28): 17391-8. Abstract: Myeloperoxidase secreted by phagocytes in the artery wall may be a catalyst for lipoprotein oxidation. High density lipoprotein (HDL) oxidized by peroxidase-generated tyrosyl radical has a markedly enhanced ability to deplete cultured cells of cholesterol. We have investigated the structural modifications in tyrosylated HDL responsible for this effect. Spherical reconstituted HDL (rHDL) containing the whole apolipoprotein (apo) fraction of tyrosylated HDL reproduced the ability of intact tyrosylated HDL to enhance cholesterol efflux from cholesterol-loaded human fibroblasts when reconstituted with the whole lipid fraction of either HDL or tyrosylated HDL. Free apoAI or apoAII showed no increased capacity to induce cholesterol efflux from cholesterol-loaded fibroblasts following oxidation by tyrosyl radical, either in their lipid-free forms or in rHDL. The product of oxidation of a mixture of apoAI and apoAII (1:1 molar ratio) by tyrosyl radical, however, reproduced the enhanced ability of tyrosylated HDL to induce cholesterol efflux when reconstituted with the whole lipid fraction of HDL. HDL containing only apoAI or apoAII showed no enhanced ability to promote cholesterol efflux following oxidation by tyrosyl radical, whereas HDL containing both apoAI and apoAII did. rHDL containing apoAI-apoAIImonomer and apoAI-(apoAII)2 heterodimers showed a markedly increased ability to prevent the accumulation of LDL-derived cholesterol mass by sterol-depleted fibroblasts compared with other apolipoprotein species of tyrosylated HDL. These results indicate a novel product of HDL oxidation, apoAI-apoAII heterodimers, with a markedly enhanced capacity to deplete cells of the regulatory pool of free cholesterol and total cholesterol mass. The recent observation of tyrosyl radical-oxidized LDL in vivo suggests that a similar modification of HDL would significantly enhance its ability to deplete peripheral cells of cholesterol in the first step of reverse cholesterol transport. |
| Enhanced cholesterol efflux promotion in well-trained soccer players Brites, F., J. Verona, et al. (2004), Metabolism 53(10): 1262-7. Abstract: It is widely accepted that aerobic physical activity is associated with a less atherogenic lipid and lipoprotein profile and, consequently, with a reduced cardiovascular risk. Both cross-sectional studies and prospective-interventional trials show that the most frequent modification observed consists of a slight but significant increase in high-density lipoprotein cholesterol (HDL-C) levels. Nevertheless, only few studies made an attempt to elucidate if this quantitative modification was accompanied by an improvement in any of HDL antiatherogenic functions. The purpose of this study was to evaluate the main steps of reverse cholesterol transport, the best known antiatherogenic function performed by HDL, in a group of well-trained soccer players (n = 35) in comparison to sedentary controls (n = 15). Average HDL-C levels were 12.5% higher in the sportsmen, in large part because of greater HDL2-C concentration. No statistically significant differences were observed in the other lipid- and lipoprotein-related parameters. The capacity to promote cholesterol efflux from Fu5AH cells was significantly higher in the soccer players than in the control individuals (20.5% +/- 0.4% v 15.9% +/- 1.2%, respectively, P <.001). However, lecithin:cholesterol acyltransferase (LCAT; 2.6 +/- 0.9 v 1.4 +/- 0.3%/mL.h, respectively) and cholesteryl ester transfer protein (CETP; 69.5 +/- 8.3 v 62.7 +/- 14.8%/mL.h, respectively) activities did not reach statistically significant difference between both groups. Correlation analysis showed that cholesterol efflux induced by serum samples was directly related to HDL-C (r = 0.59, P <.001), HDL2-C (r = 0.37, P <.01), and lipoprotein (Lp)A-I (r = 0.44, P <.05). On the other hand, negative correlations were observed with waist/hip ratio (r = -0.36, P <.05), low-density lipoprotein cholesterol (LDL-C; r = -0.33, P <.05), apolipoprotein B (apo B; r = -0.42, P <.05), and LpA-I;A-II (r = -0.51, P <.005). In conclusion, the well-known cardioprotective benefit of regular exercise could be based, at least in part, on a less atherogenic lipid and lipoprotein profile and an enhanced cellular cholesterol efflux. |