Primates that express CETP79, 80. Current clinical trials with niacin7 and CETP
Primates that express CETP79, 80. Current clinical trials with niacin7 and CETP inhibitors6 have named into query the hypothesis that raising HDL ALK1 Source cholesterol has beneficial effects on human LTC4 custom synthesis cardiovascular disease. The clinical trials with each other with experiments suggesting that the cholesterol acceptor activity of HDL isolated from sufferers may be a far more correct measurement of cardiovascular illness threat has led for the proposal that assessing HDL function can be much more relevant than measurements of HDL cholesterol mass9, 15, 20. In addition to growing the levels of HDL cholesterol, LXR agonist treatment 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 generating it difficult to discern the LXR-dependent modifications that increase cholesterol acceptor activity. Nonetheless, our initial analysis of HDL particle composition found improved levels of phospholipids (normalized to APOA1) inside the HDL particles purified from agonist treated animals. The phospholipid:APOA1 ratio in HDL has been shown to be an essential determining factor in predicting macrophageNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptArterioscler Thromb Vasc Biol. Author manuscript; obtainable in PMC 2015 August 01.Breevoort et al.Pageefflux. Research making use of mice and rats expressing human APOA1 indicate that the prime element of HDL that modulates cholesterol efflux is HDL phospholipid81, 82. Moreover, the correlation amongst macrophage cholesterol efflux and HDL phospholipid in human sera is stronger than with any other measured lipoprotein parameter, including HDL cholesterol, APOA1 and triglycerides48. CETP expression, on the other hand, seems to effect HDL function with out modulating phospholipid levels suggesting that various components of HDL can influence particle function. LXRs likely regulate numerous pathways that modulate HDL activity and future studies employing detailed lipidomic and proteomic approaches may be employed to additional define the LXR-dependent changes in HDL composition that regulate HDL particle function. These studies that define particle function might open the door to new therapeutic approaches for targeting HDL.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSupplementary MaterialRefer to Internet version on PubMed Central for supplementary material.AcknowledgmentsThe authors would prefer to thank Dr. Norbert Leitinger and Dr. Irena Ignatova (U. of Virginia) for comments around the manuscript and Dr.s Yuan Zhang, Steven Kliewer and David Mangelsdorf (UT Southwestern) for supplying the LXR liver knockout mice. SOURCES OF FUNDING Function in the author’s laboratory is supported by Grants to I.G.S. from the NIH (1R01HL096864-01A1) as well as 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 quickly liquid protein chromatography high density lipoprotein low density lipoprotein liver X receptor reverse cholesterol transportArterioscler Thromb Vasc Biol. Author manuscript; out there 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.
