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 question the hypothesis that raising HDL cholesterol has ALK5 Species advantageous effects on human cardiovascular disease. The clinical trials with each other with experiments suggesting that the cholesterol acceptor activity of HDL isolated from patients is often a additional correct measurement of cardiovascular disease danger has led towards the proposal that assessing HDL function might be a lot more relevant than measurements of HDL cholesterol mass9, 15, 20. As well as growing the levels of HDL cholesterol, LXR agonist treatment also increases the cholesterol acceptor activity of HDL particles that were normalized by the quantity of APOA1. HDL particles are heterogeneous in size and composition making it hard to discern the LXR-dependent modifications that increase cholesterol acceptor activity. Nonetheless, our initial evaluation of HDL particle composition located 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 a crucial determining aspect in predicting macrophageNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptArterioscler Thromb Vasc Biol. Author manuscript; available 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. In addition, the correlation amongst macrophage cholesterol efflux and HDL phospholipid in human sera is stronger than with any other measured lipoprotein parameter, like HDL cholesterol, APOA1 and triglycerides48. CETP expression, on the other hand, appears to influence HDL function without having modulating phospholipid levels suggesting that many 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 additional define the LXR-dependent adjustments 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 Web 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 offering the LXR liver knockout mice. SOURCES OF FUNDING Perform within the author’s laboratory is supported by Grants to I.G.S. from the NIH (1R01HL096864-01A1) and also 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 HDAC10 custom synthesis apolipoprotein A1 cholesteryl ester transfer protein cardiovascular disease speedy liquid protein chromatography high density lipoprotein low density lipoprotein liver X receptor reverse cholesterol transportArterioscler Thromb Vasc Biol. Author manuscript; available in PMC 2015 August 01.Breevoort et al.Page
Bradley et al. BMC Geriatrics 2014, 14:72 biomedcentral.com/1471-2318/14/RESEARCH ARTICLEOpen AccessPotentiall.
