The Experts below are selected from a list of 10344 Experts worldwide ranked by ideXlab platform
Daniel J Rader - One of the best experts on this subject based on the ideXlab platform.
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lymphatics as a new active player in Reverse Cholesterol Transport
Cell Metabolism, 2013Co-Authors: Mark L Kahn, Daniel J RaderAbstract:Reverse Cholesterol Transport (RCT), a key function of high-density lipoproteins (HDL), prevents excess Cholesterol in tissues. A study in this issue (Lim et al., 2013) suggests that lymphatic vessels are critical for normal RCT and mediate the active trans-endothelial Transport of HDL via the HDL receptor SR-BI.
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Abstract 71: Assessment of Reverse Cholesterol Transport in Vivo in Humans: A Novel Method
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Marina Cuchel, Jeffrey T. Billheimer, John S. Millar, Charles C Schwartz, Anna Raper, Rachel Ochotny, Amanda Baer, Ching Su, Björn Carlsson, Daniel J RaderAbstract:Aim: Reverse Cholesterol Transport (RCT) is one of the main atheroprotective functions of HDL; however no method exists to assess RCT in vivo in humans. We developed a macrophage-specific method us...
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update on the role of endothelial lipase in high density lipoprotein metabolism Reverse Cholesterol Transport and atherosclerosis
Circulation, 2010Co-Authors: Tatsuro Ishida, Tomoyuki Yasuda, Daniel J RaderAbstract:Endothelial lipase (EL) is a phospholipase that belongs to the lipoprotein lipase (LPL) family, which includes LPL and hepatic lipase (HL). Similar to LPL and HL, EL regulates lipoprotein metabolism, mainly high-density lipoprotein (HDL) metabolism and HDL Cholesterol (HDL-C) levels in humans and mice. Existing data strongly suggest that inhibition of EL in humans would be expected to increase the HDL-C level. However, it has not been definitively established whether the effect of EL activity on HDL-C levels translates into effects on Reverse Cholesterol Transport or atherosclerosis. The available data regarding the impact of EL expression and activity on HDL metabolism, Reverse Cholesterol Transport, and atherosclerosis are reviewed. (Circ J 2010; 74: 2263-2270)
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future therapeutic directions in Reverse Cholesterol Transport
Current Atherosclerosis Reports, 2010Co-Authors: Amit Khera, Daniel J RaderAbstract:Despite a robust inverse association between high-density lipoprotein (HDL) Cholesterol levels and atherosclerotic cardiovascular disease, the development of new therapies based on pharmacologic enhancement of HDL metabolism has proven challenging. Emerging evidence suggests that static measurement of HDL levels has inherent limitations as a surrogate for overall HDL functionality, particularly with regard to the rate of flux through the macrophage Reverse Cholesterol Transport (RCT) pathway. Recent research has provided important insight into the molecular underpinnings of RCT, the process by which excess cellular Cholesterol is effluxed from peripheral tissues and returned to the liver for ultimate intestinal excretion. This review discusses the critical importance and current strategies for quantifying RCT flux. It also highlights therapeutic strategies for augmenting macrophage RCT via three conceptual approaches: 1) improved efflux of cellular Cholesterol via targeting the macrophage; 2) enhanced Cholesterol efflux acceptor functionality of circulating HDL; and 3) increased hepatic uptake and biliary/intestinal excretion.
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fish oil promotes macrophage Reverse Cholesterol Transport in mice
Arteriosclerosis Thrombosis and Vascular Biology, 2009Co-Authors: Tomoyuki Nishimoto, George H. Rothblat, Michael A Pellizzon, Masakazu Aihara, Ioannis M Stylianou, Jeffery T Billheimer, Daniel J RaderAbstract:Objective— Fish oil (FO), and specifically omega 3 fatty acids, has favorable effects on cardiovascular outcomes. The aim of this study was to investigate the effects of FO on the process of macrophage Reverse Cholesterol Transport (RCT) in an in vivo mouse model. Methods and Results— C57BL/6J mice were fed a FO diet, whereas control mice were fed diets containing alternative sources of fats, soybean oil (SO), and coconut oil (CO) for 4 weeks. Macrophage RCT was assessed by injecting [ 3 H]Cholesterol-labeled J774 macrophages intraperitoneally into mice. After 48 hours, tissues were harvested and feces were collected. An increase in the excretion of macrophage-derived [ 3 H]-tracer recovered in fecal neutral sterols for FO-fed mice was observed (273% versus SO and 182% versus CO). FO also decreased [ 3 H]-tracer in hepatic cholesteryl ester compared to SO and CO by 76% and 56%, respectively. To specifically determine the effect of FO on the fate of HDL-derived Cholesterol, mice fed FO or SO diets were injected with HDL labeled with [ 3 H]cholesteryl oleate, and the disappearance of [ 3 H]-tracer from blood and its excretion in feces was measured. There was no significant difference in the fractional catabolic rate of [ 3 H]cholesteryl oleate-HDL between the 2 groups. However, there was a 242% increase in the excretion of HDL-derived [ 3 H]-tracer recovered in fecal neutral sterols in FO-fed mice, concordant with significantly increased expression of hepatic Abcg5 and Abcg8 mRNA. Conclusion— As measured by this tracer-based assay, FO promoted Reverse Cholesterol Transport, primarily by enhancement of the hepatic excretion of macrophage-derived and HDL-derived Cholesterol.
Gordon A Francis - One of the best experts on this subject based on the ideXlab platform.
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lal lysosomal acid lipase promotes Reverse Cholesterol Transport in vitro and in vivo
Arteriosclerosis Thrombosis and Vascular Biology, 2018Co-Authors: Kristin Bowden, Joshua A Dubland, Teddy Chan, Youhai Xu, Gregory A Grabowski, Hong Du, Gordon A FrancisAbstract:Objective— To explore the role of LAL (lysosomal acid lipase) in macrophage Cholesterol efflux and whole-body Reverse Cholesterol Transport. Approach and Results— Immortalized peritoneal macrophages from lal −/ − mice showed reduced expression of ABCA1 (ATP-binding cassette Transporter A1) and ABCG1 (ATP-binding cassette Transporter G1), reduced production of the regulatory oxysterol 27-hydroxyCholesterol, and impaired suppression of Cholesterol synthesis on exposure to acetylated low-density lipoprotein when compared with lal +/+ macrophages. LAL-deficient mice also showed reduced hepatic ABCG5 (ATP-binding cassette Transporter G5) and ABCG8 (ATP-binding cassette Transporter G8) expression compared with lal +/+ mice. LAL-deficient macrophages loaded with [ 3 H]-cholesteryl oleate-labeled acetylated low-density lipoprotein showed impaired efflux of released [ 3 H]-Cholesterol to apoA-I (apolipoprotein A-I), with normalization of [ 3 H]-cholesteryl ester levels and partial correction of ABCA1 expression and Cholesterol efflux to apoA-I when treated with exogenous rhLAL (recombinant human LAL protein). LAL-deficient mice injected intraperitoneally with lal −/− macrophages Cholesterol loaded and labeled in the same way exhibited only 1.55±0.35% total injected [ 3 H]-Cholesterol counts appearing in the feces for 48 h (n=30), compared with 5.38±0.92% in lal +/+ mice injected with labeled lal +/+ macrophages (n=27), P −/− macrophages into lal +/+ mice resulted in a significant increase in Reverse Cholesterol Transport (2.60±0.46% of 3 H-Cholesterol counts in feces at 48 hours [n=19]; P −/− mice). Conclusions— These results indicate a critical role for LAL in promoting both macrophage and whole-body Reverse Cholesterol Transport and the ability of supplemental LAL to be taken up and correct Reverse Cholesterol Transport in vivo.
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Oxysterol generation and liver X receptor-dependent Reverse Cholesterol Transport: Not all roads lead to Rome
Molecular and Cellular Endocrinology, 2013Co-Authors: Parmeet Singh Pannu, Sima Allahverdian, Gordon A FrancisAbstract:Cell Cholesterol metabolism is a tightly regulated process, dependent in part on activation of nuclear liver X receptors (LXRs) to increase expression of genes mediating removal of excess Cholesterol from cells in the Reverse Cholesterol Transport pathway. LXRs are thought to be activated predominantly by oxysterols generated enzymatically from Cholesterol in different cell organelles. Defects resulting in slowed release of Cholesterol from late endosomes and lysosomes or reduction in sterol-27-hydroxylase activity lead to specific blocks in oxysterol production and impaired LXR-dependent gene activation. This block does not appear to be compensated by oxysterol production in other cell compartments. The purpose of this review is to summarize current knowledge about oxysterol-dependent activation by LXR of genes involved in Reverse Cholesterol Transport, and what these defects of cell Cholesterol homeostasis can teach us about the critical pathways of oxysterol generation for expression of LXR-dependent genes. © 2012 Elsevier Ireland Ltd.
Gregory A Grabowski - One of the best experts on this subject based on the ideXlab platform.
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lal lysosomal acid lipase promotes Reverse Cholesterol Transport in vitro and in vivo
Arteriosclerosis Thrombosis and Vascular Biology, 2018Co-Authors: Kristin Bowden, Joshua A Dubland, Teddy Chan, Youhai Xu, Gregory A Grabowski, Hong Du, Gordon A FrancisAbstract:Objective— To explore the role of LAL (lysosomal acid lipase) in macrophage Cholesterol efflux and whole-body Reverse Cholesterol Transport. Approach and Results— Immortalized peritoneal macrophages from lal −/ − mice showed reduced expression of ABCA1 (ATP-binding cassette Transporter A1) and ABCG1 (ATP-binding cassette Transporter G1), reduced production of the regulatory oxysterol 27-hydroxyCholesterol, and impaired suppression of Cholesterol synthesis on exposure to acetylated low-density lipoprotein when compared with lal +/+ macrophages. LAL-deficient mice also showed reduced hepatic ABCG5 (ATP-binding cassette Transporter G5) and ABCG8 (ATP-binding cassette Transporter G8) expression compared with lal +/+ mice. LAL-deficient macrophages loaded with [ 3 H]-cholesteryl oleate-labeled acetylated low-density lipoprotein showed impaired efflux of released [ 3 H]-Cholesterol to apoA-I (apolipoprotein A-I), with normalization of [ 3 H]-cholesteryl ester levels and partial correction of ABCA1 expression and Cholesterol efflux to apoA-I when treated with exogenous rhLAL (recombinant human LAL protein). LAL-deficient mice injected intraperitoneally with lal −/− macrophages Cholesterol loaded and labeled in the same way exhibited only 1.55±0.35% total injected [ 3 H]-Cholesterol counts appearing in the feces for 48 h (n=30), compared with 5.38±0.92% in lal +/+ mice injected with labeled lal +/+ macrophages (n=27), P −/− macrophages into lal +/+ mice resulted in a significant increase in Reverse Cholesterol Transport (2.60±0.46% of 3 H-Cholesterol counts in feces at 48 hours [n=19]; P −/− mice). Conclusions— These results indicate a critical role for LAL in promoting both macrophage and whole-body Reverse Cholesterol Transport and the ability of supplemental LAL to be taken up and correct Reverse Cholesterol Transport in vivo.
P E Fielding - One of the best experts on this subject based on the ideXlab platform.
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molecular physiology of Reverse Cholesterol Transport
Journal of Lipid Research, 1995Co-Authors: Christopher J. Fielding, P E FieldingAbstract:: Reverse Cholesterol Transport (RCT) is the pathway by which peripheral cell Cholesterol can be returned to the liver for catabolism. Evidence of specific functions for molecular structures within individual plasma lipoprotein species has rapidly accumulated from recent studies using molecular and cellular physiology techniques. The removal of Cholesterol from cells, like its delivery, appears to be specific and well regulated. Although further research will be needed, RCT can now be understood in molecular terms.
George H. Rothblat - One of the best experts on this subject based on the ideXlab platform.
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high density lipoprotein heterogeneity and function in Reverse Cholesterol Transport
Current Opinion in Lipidology, 2010Co-Authors: George H. Rothblat, Michael C PhillipsAbstract:Purpose of reviewHDL is a cardioprotective lipoprotein, at least in part, because of its ability to mediate Reverse Cholesterol Transport (RCT). It is becoming increasingly clear that the antiatherogenic effects of HDL are not only dependent on its concentration in circulating blood but also on its
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fish oil promotes macrophage Reverse Cholesterol Transport in mice
Arteriosclerosis Thrombosis and Vascular Biology, 2009Co-Authors: Tomoyuki Nishimoto, George H. Rothblat, Michael A Pellizzon, Masakazu Aihara, Ioannis M Stylianou, Jeffery T Billheimer, Daniel J RaderAbstract:Objective— Fish oil (FO), and specifically omega 3 fatty acids, has favorable effects on cardiovascular outcomes. The aim of this study was to investigate the effects of FO on the process of macrophage Reverse Cholesterol Transport (RCT) in an in vivo mouse model. Methods and Results— C57BL/6J mice were fed a FO diet, whereas control mice were fed diets containing alternative sources of fats, soybean oil (SO), and coconut oil (CO) for 4 weeks. Macrophage RCT was assessed by injecting [ 3 H]Cholesterol-labeled J774 macrophages intraperitoneally into mice. After 48 hours, tissues were harvested and feces were collected. An increase in the excretion of macrophage-derived [ 3 H]-tracer recovered in fecal neutral sterols for FO-fed mice was observed (273% versus SO and 182% versus CO). FO also decreased [ 3 H]-tracer in hepatic cholesteryl ester compared to SO and CO by 76% and 56%, respectively. To specifically determine the effect of FO on the fate of HDL-derived Cholesterol, mice fed FO or SO diets were injected with HDL labeled with [ 3 H]cholesteryl oleate, and the disappearance of [ 3 H]-tracer from blood and its excretion in feces was measured. There was no significant difference in the fractional catabolic rate of [ 3 H]cholesteryl oleate-HDL between the 2 groups. However, there was a 242% increase in the excretion of HDL-derived [ 3 H]-tracer recovered in fecal neutral sterols in FO-fed mice, concordant with significantly increased expression of hepatic Abcg5 and Abcg8 mRNA. Conclusion— As measured by this tracer-based assay, FO promoted Reverse Cholesterol Transport, primarily by enhancement of the hepatic excretion of macrophage-derived and HDL-derived Cholesterol.
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selective delipidation of plasma hdl enhances Reverse Cholesterol Transport in vivo
Journal of Lipid Research, 2009Co-Authors: Frank M Sacks, George H. Rothblat, Lawrence L Rudel, Adam Paul Conner, Hassibullah Akeefe, Gerhard M Kostner, Talal Baki, Margarita De La Lleramoya, Bela F Asztalos, Timothy Jon PerlmanAbstract:Uptake of Cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed Reverse Cholesterol Transport, produces larger Cholesterol-rich HDL that transfers its Cholesterol to the liver facilitating excretion. Most HDL in plasma is Cholesterol-rich. We demonstrate that treating plasma with a novel selective delipidation procedure converts large to small HDL [HDL-selectively delipidated (HDL-sdl)]. HDL-sdl contains several Cholesterol-depleted species resembling small α, preβ-1, and other preβ forms. Selective delipidation markedly increases efficacy of plasma to stimulate ABCA1-mediated Cholesterol transfer from monocytic cells to HDL. Plasma from African Green monkeys underwent selective HDL delipidation. The delipidated plasma was reinfused into five monkeys. Preβ-1-like HDL had a plasma residence time of 8 ± 6 h and was converted entirely to large α-HDL having residence times of 13–14 h. Small α-HDL was converted entirely to large α-HDL. These findings suggest that selective HDL delipidation activates Reverse Cholesterol Transport, in vivo and in vitro. Treatment with delipidated plasma tended to reduce diet-induced aortic atherosclerosis in monkeys measured by intravascular ultrasound. These findings link the conversion of small to large HDL, in vivo, to improvement in atherosclerosis.
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inflammation impairs Reverse Cholesterol Transport in vivo
Circulation, 2009Co-Authors: Fiona C Mcgillicuddy, George H. Rothblat, Jeffrey T. Billheimer, Margarita De La Llera Moya, Christine C Hinkle, Michelle R Joshi, Elise H Chiquoine, Muredach P ReillyAbstract:Background— Inflammation is proposed to impair Reverse Cholesterol Transport (RCT), a major atheroprotective function of high-density lipoprotein (HDL). The present study presents the first integrated functional evidence that inflammation retards numerous components of RCT. Methods and Results— We used subacute endotoxemia in the rodent macrophage-to-feces RCT model to assess the effects of inflammation on RCT in vivo and performed proof of concept experimental endotoxemia studies in humans. Endotoxemia (3 mg/kg SC) reduced 3H-Cholesterol movement from macrophage to plasma and 3H-Cholesterol associated with HDL fractions. At 48 hours, bile and fecal counts were markedly reduced consistent with downregulation of hepatic expression of ABCG5, ABCG8, and ABCB11 biliary Transporters. Low-dose lipopolysaccharide (0.3 mg/kg SC) also reduced bile and fecal counts, as well as expression of biliary Transporters, but in the absence of effects on plasma or liver counts. In vitro, lipopolysaccharide impaired 3H-choles...
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Effects of nevirapine and efavirenz on HDL Cholesterol levels and Reverse Cholesterol Transport in mice
Atherosclerosis, 2008Co-Authors: Junichiro Tohyama, George H. Rothblat, Daniel J Rader, Jeffrey T. Billheimer, Ilia V. Fuki, John S. MillarAbstract:Objective The mechanism by which non-nucleoside Reverse transcriptase inhibitors (NNRTIs) increase HDL Cholesterol (HDL-C) in HIV+ patients and the benefits of this with respect to cardiovascular risk are not known. Studies were conducted to test the hypothesis that NNRTIs have a beneficial effect on HDL-C and Reverse Cholesterol Transport (RCT).
