Primates that express CETP79, 80. Recent clinical trials with niacin7 and CETP
Primates that express CETP79, 80. Current clinical trials with niacin7 and CETP inhibitors6 have called into question the hypothesis that raising HDL cholesterol has valuable effects on human cardiovascular disease. The clinical trials together with experiments suggesting that the cholesterol acceptor activity of HDL isolated from sufferers could be a far more correct measurement of cardiovascular illness threat has led towards the proposal that assessing HDL function might be a lot more relevant than measurements of HDL cholesterol mass9, 15, 20. Along with growing the levels of HDL cholesterol, LXR agonist treatment also increases the cholesterol acceptor activity of HDL particles that had been normalized by the quantity of APOA1. HDL particles are heterogeneous in size and composition producing it tough to discern the LXR-dependent modifications that boost 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 vital determining element 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 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 HD2 Purity & Documentation between macrophage cholesterol efflux and HDL phospholipid in human sera is stronger than with any other measured lipoprotein parameter, which includes HDL cholesterol, APOA1 and COX-1 Species triglycerides48. CETP expression, however, appears to influence HDL function with out modulating phospholipid levels suggesting that a number of components of HDL can influence particle function. LXRs most likely regulate various pathways that modulate HDL activity and future studies employing detailed lipidomic and proteomic approaches is often utilised to additional define the LXR-dependent alterations in HDL composition that regulate HDL particle function. These studies that define particle function may well 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 like 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 providing the LXR liver knockout mice. SOURCES OF FUNDING Function inside the author’s laboratory is supported by Grants to I.G.S. from the NIH (1R01HL096864-01A1) plus 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 disease rapidly 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.
