Reverse Cholesterol Transport Activity Research Articles

Osteoblast Demineralization Induced by Oxidized High-Density Lipoprotein via the Inflammatory Pathway Is Suppressed by Adiponectin.

Low mineralization activity by human osteoblast cells (HOBs) indicates abnormal bone remodeling that potentially leads to osteoporosis. Oxidation, the most prominent form of high-density lipoprotein (HDL) modification, is suggested to affect bone mineralization through the inflammatory pathway. Adiponectin, which possesses anti-inflammatory activity, is postulated to have the ability to suppress the detrimental effects of oxidized HDL (oxHDL). This study aimed to investigate the effects of HDL before and after oxidation on markers of mineralization and inflammation. The protective effects of adiponectin on demineralization and inflammation induced by oxHDL were also investigated. OxHDL at 100 µg/mL protein had the highest inhibitory effect on mineralization, followed by lower calcium incorporation. OxHDL also had significantly lower expression of a mineralization marker (COL1A2) and higher expression of inflammatory markers (IL-6, TNF-α, and RELA proto-oncogene, NF-κβ (p65)) compared to the unstimulated control group. These findings suggest that oxHDL reduces the mineralization activity of HOBs by increasing the expression of inflammatory markers. Interestingly, co-incubation of adiponectin and oxHDL in HOBs resulted in higher expression of mineralization markers (ALPL, COL1A2, BGLAP, and RUNX2) and significantly reduced all targeted inflammatory markers compared to the oxHDL groups. On the contrary, HDL increased the expression of mineralization markers (COL1A2 and STAT-3) and exhibited lower expression of inflammatory cytokines (IL-6 and TNF-α), proving the protective effect of HDL beyond the reverse cholesterol transport activity.

A systematic review: the appraisal of the effects of metformin on lipoprotein modification and function.

SummaryAimsMetformin is a commonly prescribed anti‐hyperglycaemic pharmacological agent, and it remains a staple in the management of type II diabetes. In addition to metformin's glucose lowering effects, research has indicated that metformin inhibits glycation‐mediated and oxidative modification of lipoprotein residues. The purpose was to discuss the effects of metformin as it relates to high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) modification.Materials and methodsThe purpose was to conduct a narrative and pragmatic review on the effects of metformin as it pertains to HDL and LDL modification.ResultsHigh‐density lipoprotein (HDL) concentration is a quantitative measure and therefore does not provide insight into its function, which is a qualitative property. Dysfunctional HDLs are unable to carry out functions normally associated with HDL because they can be modified by glycating agents. Metformin may counteract HDL dysfunction by abating HDL modification. Reductions in HDL modification may improve reverse cholesterol transport ability and thus possibly diminish cardiovascular risk. Similarly, metformin‐mediated attenuations in LDL modification may reduce their atherogenic potency.ConclusionMetformin may partially ameliorate HDL dysfunction and reduce LDL modification by inhibiting alpha‐dicarbonyl‐mediated modification of apolipoprotein residues; consequently, the results are salient because cardiovascular disease incidence may be reduced given that reverse cholesterol transport activity predicts risk, and modified LDL are proatherogenic.

Stilbenoids and cannabinoids from the leaves of Cannabis sativa f. sativa with potential reverse cholesterol transport activity.

Three new stilbenoids (1-3) and 16 known stilbenoids (4-6) and cannabinoids (7-19) were isolated from the leaves of hemp (Cannabis sativa L.). The structures of the three new compounds were identified as α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-3-isopentenylstilbene (HM1), α,α'-dihydro-3,4',5-trihydroxy-4-methoxy-2,6-diisopentenylstilbene (HM2), and α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-2',3-diisopentenylstilbene (HM3) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known α,α'-dihydro-3,4',5-trihydroxy-4,5'-diisopentenylstilbene (5) and combretastatin B-2 (6) were isolated for the first time from C. sativa f. sativa. These isolated compounds exhibited cytotoxic effects on human cancer cells via inhibiting the proliferation of cancer cells and inducing cell death. Among them, compounds 4, 5, 10, 12, 13, 15, and 19 displayed broad-spectrum cytotoxicity, and 1, 7, and 11 displayed selectivity in inhibition efficiency on MCF-7 and A549 cells, which suppressed the proliferation of cancer cells significantly by inducing cell death. The effects of compounds 1-3 on improving reverse cholesterol transport (RCT) were evaluated by isotope-tracing and western blotting. Results showed that the three stilbenoids showed a cytotoxicity above 1.0 mg L-1, especially that of HM3. They could improve [3H]-cholesterol efflux from Raw 264.7 macrophages to high density lipoproteins by enhancing the protein expression of ABCG1 and SR-B1, and HM1 and HM2 showed a significant difference compared with fenofibrate at 1.0 mg L-1. The three stilbenoids could also significantly improve the protein expression of ABCA1. Further study on HepG2 cells indicated that they improve the protein expression of LDLR, SR-B1 and CYP7A1, especially that of HM1 and HM3. However, they showed no significant effect on PCSK9. The above results indicated that these stilbenoids may elevate the transfer of cholesterol to hepatocytes by improving the protein expression of SR-B1 and LDLR, and the synthesis of bile acid by increasing the protein expression of CYP7A1. In conclusion, HM1 showed lower cytotoxicity and higher activity in improving the RCT-related protein expression. Our study suggests that it may be explored as a novel lipid-lowering drug and as a beneficial ingredient in health functional foods and pharmaceuticals.

Abstract 334: The LXRβ Selective Agonist, VTP-38443, Significantly Decreases Plaque Cholesterol Ester Content and Inflammation in a Murine Model of Accelerated Atherosclerosis

The ligand-activated transcription factors LXRα and LXRβ are important regulators of cholesterol metabolism and inflammation. Activation of LXR was previously shown to inhibit atherosclerosis in animal models through activation of reverse cholesterol transport (RCT) and suppression of vascular inflammation. VTP-38443 is a potent selective and orally bioavailable modulator of LXRβ that is being pursued for the prevention of subsequent vascular events following an acute coronary syndrome (ACS) episode. VTP-38443 is a potent binder (Ki=12 nM) and activator (EC50=17 nM) of LXRβ. It is ~20x selective for LXRβ versus LXRβ in both binding and activation. In primary human cells, it induces the expression of the cholesterol efflux pumps ABCA1 and ABCG1, markers of RCT, and promotes cholesterol efflux from human fibroblasts at low concentrations (EC50 = 14 nM). Orally dosed VTP-38443 demonstrates robust induction of ABCA1 and ABCG1 in mice (ED50 < 0.3 mg/kg) and primates (ED50 < 0.1 mg/kg). Based on this robust activity, VTP-38443 was tested in the apoE -/- carotid artery ligated mouse model, an accelerated atherosclerosis model. ApoE-/- mice (9 week) were fed a Western diet for 2 weeks at which point the left common carotid artery was ligated. Mice remained on the Western diet for 2 weeks post-surgery and were dosed BID with VTP-38443 (0.05, 0.2 and 1 mg/kg/dose) or a non-selective LXR agonist, TO90137 (20 mg/kg/day) during this time. Plasma cholesterol and TGs were measured as were cholesterol esters and FDG-6-phosphate, a biomarker of plaque inflammation, in the carotid plaques. VTP-38443 gave a dose-dependent reduction in plasma cholesterol (35% at 1 mg/kg) and a modest dose-dependent increase in plasma TGs ranging from 5% to 45% of the TG increase seen with TO90137. Plaque analysis showed a highly significant decrease in carotid cholesterol ester content at all doses, achieving >90% reduction at the highest dose. In addition, there was a significant reduction (~40-50%) in FDG-6 phosphate at all doses of VTP-38443, indicating a decrease in vascular inflammation. These data indicate that LXRβ activation may decrease plaque cholesterol content and reduce plaque inflammation in ACS.

Treating low high-density lipoprotein cholesterol: what is the evidence?

Epidemiological studies have shown an inverse association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) risk. However, genetic and interventional studies have failed to consistently support this relationship. There is an increasing body of evidence that the function of HDL, including its antiatherogenic properties and its reverse cholesterol transport activity, has a greater impact on CVD risk compared with levels of HDL alone. Targeting HDL has become a growing interest. Nevertheless, raising HDL pharmacologically has failed to show a considerable, if any, impact on cardiovascular outcome. Efforts should focus on improving HDL quality in addition to raising HDL levels when developing new therapies. Ongoing and future research will help determine the most safe and effective approach to improve cardiovascular outcome and establish the safety, efficacy and impact on atherosclerosis of the emerging HDL-raising therapies.

Cyanidin, a natural flavonoid, is an agonistic ligand for liver X receptor alpha and beta and reduces cellular lipid accumulation in macrophages and hepatocytes

Cyanidin, a natural flavonoid abundant in fruits and vegetables, is known to regulate cellular lipid metabolism; however, its underlying mechanism of action and protein targets remain unknown. Here, the ligand binding activity of cyanidin on liver X receptors (LXRs) was investigated utilizing surface plasmon resonance and time-resolved fluorescence energy transfer (TR-FRET) analyses. LXRs are nuclear receptors which function as critical transcription factors in the regulation of cellular lipid and glucose metabolism. This includes the stimulation of high-density-lipoprotein synthesis and activation of reverse cholesterol transport. The present findings show that cyanidin induces the transactivation of LXRs and binds directly to the ligand-binding domain of both LXRα and LXRβ with dissociation constants of 2.2 and 73.2μM, respectively. Cell-free FRET analysis demonstrated that cyanidin induces the recruitment of co-activator peptide for LXRα and LXRβ with EC50 of 3.5μM and 125.2μM, respectively. In addition, intracellular cholesterol and triglyceride (TG) concentrations were reduced in macrophages following cyanidin stimulation. In cultured hepatocytes, cyanidin mildly induced SREBP1c gene expression but marginally affected cellular TG concentrations as well as reduced cellular cholesterol accumulations which activated the expression of genes for reverse cholesterol transport. Two cyanidin metabolites, procatechic acid and phloroglucinaldehyde, did not directly bind or activate LXRs. These results demonstrate that cyanidin is a direct ligand for both LXRα and LXRβ, suggesting that cyanidin may operate, at least in part, through modulation of cellular LXR activity.

Overview of the pharmacology and physiological roles of P2Y receptors

AbstractThe release of nucleotides in extracellular fluids can result from cell necrosis, exocytosis of secretory granules (such as platelet‐dense granules), vesicular trafficking, or efflux through membrane channels. Once in the extracellular fluids, nucleotides are rapidly degraded by ectonucleotidases, such as CD39 and CD73, that transform ATP sequentially into ADP, AMP and finally adenosine. Extracellular nucleotides act on two families of receptors: the ionotropic P2X receptors and the G‐protein‐coupled P2Y receptors. There are eight genuine P2Y receptor subtypes encoded by distinct genes that can be subdivided in two structurally distinct subfamilies: P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 on one hand and P2Y12, P2Y13, and P2Y14 on the other hand. Whereas P2X receptors are receptors of ATP, the different P2Y receptors are activated by distinct nucleotides, diphosphates or triphosphates, purines or pyrimidines, some of them being conjugated to sugars. The most striking action of nucleotides mediated by P2Y receptors is the aggregation of platelets by ADP that involves a cooperation between P2Y1 and P2Y12. The only drugs targeting a P2Y receptor currently on the market are P2Y12 antagonists used as antiplatelet agents: ticlopidine, clopidogrel, prasugrel, and ticagrelor. However, gene silencing techniques have been instrumental in establishing new unexpected functions of P2Y receptors, such as the role of P2Y2 receptors in leukocyte chemotaxis and tissue infiltration, the attraction of microglia by P2Y12 and the stimulation of their phagocytic activity by P2Y6, and the activation of reverse cholesterol transport by P2Y13 expressed on hepatocytes. WIREs Membr Transp Signal 2012, 1:581–588. doi: 10.1002/wmts.44For further resources related to this article, please visit the WIREs website.

Modification of High Density Lipoprotein by Myeloperoxidase Generates a Pro-inflammatory Particle

High density lipoprotein (HDL) is the major atheroprotective particle in plasma. Recent studies demonstrate that myeloperoxidase (MPO) binds to HDL in vivo, selectively targeting apolipoprotein A1 (apoA1) of HDL for oxidative modification and concurrent loss in cholesterol efflux and lecithin cholesterol acyl transferase activating activities, generating a "dysfunctional HDL" particle. We now show that (patho)physiologically relevant levels of MPO-catalyzed oxidation result in loss of non-cholesterol efflux activities of HDL including anti-apoptotic and anti-inflammatory functions. One mechanism responsible is shown to involve the loss of modified HDL binding to the HDL receptor, scavenger receptor B1, and concurrent acquisition of saturable and specific binding to a novel unknown receptor independent of scavenger receptors CD36 and SR-A1. HDL modification by MPO is further shown to confer pro-inflammatory gain of function activities as monitored by NF-kappaB activation and surface vascular cell adhesion molecule levels on aortic endothelial cells exposed to MPO-oxidized HDL. The loss of non-cholesterol efflux activities and the gain of pro-inflammatory functions requires modification of the entire particle and can be recapitulated by oxidation of reconstituted HDL particles comprised of apoA1 and nonoxidizable phosphatidylcholine species. Multiple site-directed mutagenesis studies of apoA1 suggest that the pro-inflammatory activity of MPO-modified HDL does not involve methionine, tyrosine, or tryptophan, oxidant-sensitive residues previously mapped as sites of apoA1 oxidation within human atheroma. Thus, MPO-catalyzed oxidation of HDL results not only in the loss of classic atheroprotective reverse cholesterol transport activities of the lipoprotein but also both the loss of non-cholesterol efflux related activities and the gain of pro-inflammatory functions.

Liver X Receptor Ligands in the Rhesus Macaque Corpus Luteum Throughout the Luteal Phase: Implications for Reverse Cholesterol Transport Activity.

Liver X Receptor Ligands in the Rhesus Macaque Corpus Luteum Throughout the Luteal Phase: Implications for Reverse Cholesterol Transport Activity.

Age-Associated Decrease of High-Density Lipoprotein-Mediated Reverse Cholesterol Transport Activity

High-density lipoproteins (HDL) are considered atheroprotective in contrast to low-density lipoproteins (LDL), which are atherogenic in their oxidized form. A growing body of evidence suggests that HDL exert part of their antiatherogenic effect by counteracting LDL oxidation as well as their proinflammatory effect. However, a number of studies, carried over the past 30 years, have shown that cholesterol efflux plays a major role in the atheroprotective effects of HDL and cholesterol homeostasis. These studies have further identified the scavenger receptor type B-I (SR-BI), the adenosine triphosphate (ATP)-binding cassette transporters ATP-binding cassette subfamily A1 (ABCA1), ATP-binding cassette subfamily G1 (ABCG1) and ABCG4, the liver X receptor/retinoid X receptor (LXR/RXR) and peroxisome proliferator-activated receptorgamma(PPAR gamma) transcription factors, the HDL components apolipoprotein A-I (apoA-I), lecithin-cholesterol acyltransferase (LCAT), and phospholipids as additional mediators of cholesterol transport. Cholesterol efflux occurs via three independent pathways: (1) aqueous diffusion, (2) nonspecific efflux via SR-BI receptors, and (3) specific efflux via cholesterol-responsive members of the ABC superfamily. Whereas aqueous diffusion and scavenger receptor class B, type I (SR-BI)-mediated efflux transport free cholesterol to a wide variety of cholesterol acceptors (particles containing phospholipids, HDL, and lipidated apo-lipoproteins; LDL, etc), the ABCA1 pathway mediates the transport of cholesterol in a unidirectional manner, mainly to lipid-poor apoA-I. In contrast, the ABCG1 pathway is responsible for the transport of cholesterol to all the subfamily members of HDL. Although HDL-mediated cholesterol efflux is apoA-I-dependent, recent studies have suggested an involvement of the enzyme paraoxonase 1 (PON1). Cholesterol efflux is carried on by a number of factors such as genetic mutations, smoking, stress, and high-fat diets. It is attenuated with aging due to changes in the composition and structure of HDL, especially the phosphatidylcholine/sphingomyelin ratio, the fluidity of the phospholipidic layer, the concentration of apoA-I, and the activity of PON1. This review summarizes the findings that cholesterol homeostasis is disrupted with aging as a consequence of dysfunctional cholesterol efflux and the impairment of physiological functions.

Age-Associated Decrease of High-Density Lipoprotein-Mediated Reverse Cholesterol Transport Activity

Age-Associated Decrease of High-Density Lipoprotein-Mediated Reverse Cholesterol Transport Activity

Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8

Liver X receptor (LXR) agonists increase both total fecal sterol excretion and macrophage-specific reverse cholesterol transport (RCT) in vivo. In this study, we assessed the effects of ABCG5/G8 deficiency as well as those of LXR agonist-induction of RCT from macrophages to feces in vivo. A [(3)H]cholesterol-labeled macrophage cell line was injected intraperitoneally into ABCG5/G8-deficient (G5/G8(-/-)), heterozygous (G5G8(+/-)), and wild-type G5/G8(+/+) mice. G5/G8(-/-)mice presented increased radiolabeled HDL-bound [(3)H]cholesterol 24 h after the label injection. However, the magnitude of macrophage-derived [(3)H]cholesterol in liver and feces did not differ between groups. A separate experiment was conducted in G5G8(+/+) and G5G8(-/-) mice treated with or without the LXR agonist T0901317. Treatment with T0901317 increased liver ABCG5/G8 expression, which was associated with a 2-fold increase in macrophage-derived [(3)H]cholesterol in feces of G5/G8(+/+) mice. However, T0901317 treatment had no effect on fecal [(3)H]cholesterol excretion in G5G8(-/-) mice. Additionally, LXR activation stimulated the fecal excretion of labeled cholesterol after an intravenous injection of HDL-[(3)H]cholesteryl oleate in G5/G8(+/+) mice, but failed to enhance fecal [(3)H]cholesterol in G5/G8(-/-) mice. Our data provide direct in vivo evidence of the crucial role of ABCG5 and ABCG8 in LXR-mediated induction of macrophage-specific RCT.

HDL: Close to Our Memories?

The last decade has witnessed an explosion in studies of the role of lipoproteins in brain function. Neurons require a continuous supply of lipids for membrane synthesis and acetylcholine production. Indeed, the brain is a site of intense lipid turnover—even though the central nervous system (CNS) accounts for only 2.1% of body weight, it contains 23% of total body cholesterol.1 Lipid metabolism in the brain is tightly controlled locally, as plasma lipoproteins are shielded from the brain by the blood-brain barrier. Although neuronal cells are capable of de novo synthesis of a wide spectrum of molecular species of lipids, they rely heavily on exogenous sources and readily bind and internalize lipoproteins of the extracellular fluid.2 Equally, neurons need to dispose of excess lipids; lipoprotein-mediated lipid transport is therefore bidirectional and includes cellular efflux of cholesterol.3 See accompanying article on page 1556 Human cerebrospinal fluid (CSF) primarily contains spherical lipoproteins of approximately 10 to 12 nm in diameter with hydrated density in the range 1.063 to 1.25 g/mL, thereby resembling HDL in human plasma.3,4⇓ Lipid concentrations in CSF are however much lower (eg, 300- to 400-fold for total cholesterol and phospholipids) as compared to the plasma compartment.4 Apolipoproteins (apo) E and A-I are the major apolipoproteins in human CSF (typical concentration range: 0.1 to 0.4 mg/dL3,4⇓), with apoA-II, A-IV, J, D, C-II, C-III, C-IV, and H equally present.3,4⇓ Importantly, CSF lipoproteins carry amyloid-β (Aβ), a 39- to 43-aa peptide produced in neuronal cells, which is the major component of senile amyloid plaques.5 The metabolism of CSF lipoproteins remains poorly characterized but seems to be distinct from that of plasma lipoproteins. ApoE-rich HDL are synthesized locally in CNS and secreted by astrocytes as discoidal complexes enriched in free cholesterol.6 High …

Interplay of Oxygen, Vitamin E, and Carotenoids in Radical Reactions following Oxidation of Trp and Tyr Residues in Native HDL3 Apolipoproteins. Comparison with LDL. A Time-Resolved Spectroscopic Analysis

It has been recently shown that the inhibition of apolipoprotein A-I (apoAI) reverse cholesterol transport activity during oxidation of HDL by myeloperoxidase may involve myeloperoxidase electron transfer pathways other than those leading to tyrosine chlorination. To better understand how such mechanisms might be initiated, the role of semioxidized Tyr and Trp residues in loss of apoAI and apolipoprotein A-II (apoAII) integrity has been assessed using selective Trp and Tyr one-electron oxidation by *Br2(-) radical-anions in HDL3 as well as in unbound apoAI and apoAII. Behavior of these radicals in apolipoprotein B of LDL has also been assessed. Formation of semioxidized Tyr in HDL3 is followed by partial repair during several milliseconds via reaction with endogenous alpha-tocopherol to form the alpha-tocopheroxyl radical. Subsequently, 2% of alpha-tocopheroxyl radical is repaired by HDL3 carotenoids. With LDL, a faster repair of semioxidized Tyr by alpha-tocopherol is observed, but carotenoid repair of alpha-tocopheroxyl radical is not. Only a small fraction of HDL3 particles contains alpha-tocopherol and carotenoids, which explains limited repair of semioxidized Tyr by alpha-tocopherol. All LDL particles normally contain multiple alpha-tocopherol and carotenoid molecules, and the lack of repair of alpha-tocopheroxyl radical by carotenoids probably results from hindered mobility of carotenoids in the lipid core. Western blots of gamma-irradiated HDL3 comparable to those reported for apoAI myeloperoxidase oxidation show that the incomplete repair of semioxidized Tyr and Trp induces apoAI and apoAII permanent damage including formation of a heterodimer of one apoAI with a monomeric apoAII at about 36 kDa.

Oxidized low-density lipoprotein: A double-edged sword on atherosclerosis

It is well known that atherosclerosis is closely related to lipoprotein metabolism, particularly to the low density lipoprotein (LDL). LDL becomes atherogenic after undergoing oxidation by vascular cells, that transform them into highly bioreactive oxidized LDL (oxLDL). oxLDL is generally though to be involved in foam cell formation, and trigger an array of proatherogenic events. However, there are accumulating evidences that low levels of oxLDL can be atheroprotective through its cytoprotection, modulation of immunity and activation of reverse cholesterol transport. Thus, oxLDL may exert biphasic effects on atherosclerosis, just like a doubled-edged sword.

Localization of Nitration and Chlorination Sites on Apolipoprotein A-I Catalyzed by Myeloperoxidase in Human Atheroma and Associated Oxidative Impairment in ABCA1-dependent Cholesterol Efflux from Macrophages

We recently reported that apolipoprotein A-I (apoA-I), the major protein component of high density lipoprotein, is a selective target for myeloperoxidase (MPO)-catalyzed nitration and chlorination in both and serum of subjects with cardiovascular disease. We further showed that the extent of both apoA-I nitration and chlorination correlated with functional impairment in reverse cholesterol transport activity of the isolated lipoprotein. Herein we used tandem mass spectrometry to map the sites of MPO-mediated apoA-I nitration and chlorination in vitro and in vivo and to relate the degree of site-specific modifications to loss of apoA-I lipid binding and cholesterol efflux functions. Of the seven tyrosine residues in apoA-I, Tyr-192, Tyr-166, Tyr-236, and Tyr-29 were nitrated and chlorinated in MPO-mediated reactions. Site-specific liquid chromatography-mass spectrometry quantitative analyses demonstrated that the favored modification site following exposure to MPO-generated oxidants is Tyr-192. MPO-dependent nitration and chlorination both proceed with Tyr-166 as a secondary site and with Tyr-236 and Tyr-29 modified only minimally. Parallel functional studies demonstrated dose-dependent losses of ABCA1-dependent cholesterol acceptor and lipid binding activities with apoA-I modification by MPO. Finally tandem mass spectrometry analyses showed that apoA-I in human atherosclerotic tissue is nitrated at the MPO-preferred sites, Tyr-192 and Tyr-166. The present studies suggest that site-specific modifications of apoA-I by MPO are associated with impaired lipid binding and ABCA1-dependent cholesterol acceptor functions, providing a molecular mechanism that likely contributes to the clinical link between MPO levels and cardiovascular disease risk.

INFLUENCE OF STRENUOUS ENDURANCE EXERCISE ON CHOLESTERYL ESTER TRANSFER PROTEIN AND HDL METABOLISM IN SERUM 169

This study was conducted to clarify the effect of a single bout of strenuous endurance exercise on reverse cholesterol transport through HDL. Thirty-two male triathletes (35.7±8.3yr.) who participated in the '95 Ironman Japan in Lake Biwa (3.8km swim, 180.2km bike, 42.2km run, average duration time: 10hr. 24min.) were examined. Blood samples were taken before, immediately after and one day after the race. Significant increase in serum HDL cholesterol (HDL-C) was observed immediately after the race (66.4 ± 16.6mg/dl to 70.1 ± 17.6mg/dl: p<0.01). However, there was a significant plasma volume change immediately and one day after the race (-7.0% and +4.6%, respectively). If the plasma volume changes were normalized, HDL-C revealed a significant increase one day after the race (+5.5%). HDL-C/(apoA-I+apoA-II) also showed a significant increase one day after the race. This indicates that strenuous exercise altered HDL to a cholesterol rich particle. Serum cholesteryl ester transfer protein (CETP) activity decreased significantly immediately and one day after the race.Table Moreover, there were significant negative correlations between serum CETP activity and HDL-C/(apoA-I+apoA-II) immediately after and one day after the race (p<0.05). These results suggest that CETP mediated cholesterol transfer was obstructed, therefore, cholesterol might accumulate in HDL after strenuous exercise. We conclude that a single bout of strenuous endurance exercise hindered HDL in its reverse cholesterol transport activity by reduction of CETP.

Decreased Reverse Cholesterol Transport Activity of Glycated High-Density Lipoproteins

Decreased Reverse Cholesterol Transport Activity of Glycated High-Density Lipoproteins