Primates that express CETP79, 80. Recent clinical trials with niacin7 and CETP
Primates that express CETP79, 80. Recent clinical trials with niacin7 and CETP inhibitors6 have known as into query the hypothesis that raising HDL cholesterol has useful effects on human cardiovascular disease. The clinical trials together with experiments suggesting that the cholesterol acceptor activity of HDL isolated from sufferers may be a much more correct measurement of cardiovascular disease threat has led to the proposal that assessing HDL function may be more relevant than measurements of HDL cholesterol mass9, 15, 20. Along with escalating the levels of HDL cholesterol, LXR agonist remedy also increases the cholesterol acceptor activity of HDL particles that have been normalized by the quantity of APOA1. HDL particles are heterogeneous in size and composition creating it tough to discern the LXR-dependent modifications that increase cholesterol acceptor activity. Nonetheless, our initial analysis of HDL particle composition found enhanced levels of phospholipids (normalized to APOA1) within the HDL particles purified from agonist treated animals. The phospholipid:APOA1 ratio in HDL has been shown to become a crucial determining issue in predicting macrophageNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptArterioscler Thromb Vasc Biol. Author manuscript; out there in PMC 2015 August 01.Breevoort et al.Pageefflux. Studies applying mice and rats expressing human APOA1 indicate that the prime component of HDL that modulates cholesterol efflux is HDL phospholipid81, 82. Moreover, the correlation in between macrophage cholesterol efflux and HDL phospholipid in human sera is stronger than with any other measured Fas site lipoprotein parameter, like HDL cholesterol, APOA1 and triglycerides48. CETP expression, however, seems to influence HDL function without modulating phospholipid levels suggesting that numerous elements of HDL can influence particle function. LXRs likely regulate several pathways that modulate HDL activity and future studies employing detailed lipidomic and proteomic approaches might be made use of to further define the LXR-dependent alterations in HDL composition that regulate HDL particle function. These studies that define particle function may perhaps open the door to new therapeutic approaches for targeting HDL.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSupplementary ALK4 Synonyms MaterialRefer to Web version on PubMed Central for supplementary material.AcknowledgmentsThe authors would like to thank Dr. Norbert Leitinger and Dr. Irena Ignatova (U. of Virginia) for comments on the manuscript and Dr.s Yuan Zhang, Steven Kliewer and David Mangelsdorf (UT Southwestern) for providing the LXR liver knockout mice. SOURCES OF FUNDING Function within the author’s laboratory is supported by Grants to I.G.S. from the NIH (1R01HL096864-01A1) along with the AHA (13GRNT1650022).Nonstandard Abbreviations and AcronymsABCA1 ABCG1 ABCG5 ABCG8 APOA1 CETP CVD FPLC HDL LDL LXR RCT ATB binding cassette transporter A1 ATB binding cassette transporter G1 ATB binding cassette transporter G5 ATB binding cassette transporter G8 apolipoprotein A1 cholesteryl ester transfer protein cardiovascular illness quick liquid protein chromatography high density lipoprotein low density lipoprotein liver X receptor reverse cholesterol transportArterioscler Thromb Vasc Biol. Author manuscript; obtainable in PMC 2015 August 01.Breevoort et al.Web page
Bradley et al. BMC Geriatrics 2014, 14:72 biomedcentral.com/1471-2318/14/RESEARCH ARTICLEOpen AccessPotentiall.
