HDL and cholesterol: life after the divorce?

Vickers, Kasey C.; Remaley, Alan T.

doi:10.1194/jlr.r035964

Cited by 81 publications

(58 citation statements)

References 96 publications

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“…In addition to the variety of proteins, a variety of lipids are also carried by HDL, and some of them are or can be transformed to potent bioactive molecules (Vickers and Remaley 2014). Furthermore, HDL carries and transports fat soluble vitamins, steroid hormones, carotenoids, as well as numerous more polar metabolites such as heneicosanoic acid, pentitol, and oxalic acid which were found to be significantly correlated with insulin resistance (Vickers and Remaley 2014).…”

Section: Complexity Of Hdlmentioning

confidence: 99%

HDL Biogenesis, Remodeling, and Catabolism

Zannis

Fotakis

Κούκος

et al. 2014

Handbook of Experimental Pharmacology

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In this chapter, we review how HDL is generated, remodeled, and catabolized in plasma. We describe key features of the proteins that participate in these processes, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism. The biogenesis of HDL initially requires functional interaction of apoA-I with the ATP-binding cassette transporter A1 (ABCA1) and subsequently interactions of the lipidated apoA-I forms with lecithin/cholesterol acyltransferase (LCAT). Mutations in these proteins either prevent or impair the formation and possibly the functionality of HDL. Remodeling and catabolism of HDL is the result of interactions of HDL with cell receptors and other membrane and plasma proteins including hepatic lipase (HL), endothelial lipase (EL), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), apolipoprotein M (apoM), scavenger receptor class B type I (SR-BI), ATP-binding cassette transporter G1 (ABCG1), the F1 subunit of ATPase (Ecto F1-ATPase), and the cubulin/megalin receptor. Similarly to apoA-I, apolipoprotein E and apolipoprotein A-IV were shown to form discrete HDL particles containing these apolipoproteins which may have important but still unexplored functions. Furthermore, several plasma proteins were found associated with HDL and may modulate its biological functions. The effect of these proteins on the functionality of HDL is the topic of ongoing research.

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Section: Complexity Of Hdlmentioning

confidence: 99%

HDL Biogenesis, Remodeling, and Catabolism

Zannis

Fotakis

Κούκος

et al. 2014

Handbook of Experimental Pharmacology

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“…243 In fact, its broad binding capacity has motivated the generation of reconstituted HDLs for the detoxification of lipopolysaccharides in sepsis as well as for the delivery of drugs for therapy or diagnostic imaging. 244, 245 However, the binding of some exogenous molecules or endogsure as well as impaired healing of denuded arteries by EPCs.…”

Section: Post-translational Modifications Of Proteinsmentioning

confidence: 99%

High-Density Lipoproteins

Annema

Eckardstein

2013

Circ J

144

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk. 2433Multifunctional but Vulnerable HDL munication of results. 15 As yet, clinical and epidemiological studies have come to discrepant and inconsistent conclusions on the prognostic performance of HDL subclasses differentiated by size. 14,20-24 Sometimes the associations of cardiovascular risk with the various HDL subclass concentrations were not stronger than with HDL-C, 20,21 and even if so, the associations with size were discrepant: significant associations with risk of cardiovascular events or stroke were found for small HDL in some studies, 22,23 but for medium-sized HDL 21,23 or large HDL 14,20,21,24 in others.Previous proteomic, lipidomic, and transcriptomic studies revealed a much greater structural complexity of HDLs: 80 different proteins, 25,26 more than 200 lipid species, 27,28 and several microRNAs 29,30 have been identified in HDL isolated from plasma by either ultracentrifugation, gel filtration, or immunoaffinity chromatography (Figure 1). Among the proteins, apoA-II is present in HDLs at the highest concentration after that of apoA-I and has been investigated for its cardiovascular risk association by several studies. In contrast to initial findings, large prospective studies did not find any significant differences in the risk association between apoA-II-containing and apoA-II-free HDL. [15][16][17] Despite their much lower concentrations relative to the 2 major proteins apoA-I and apoA-II and relative to the major lipids, many quantitatively minor componen...

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“…HDL is a collection of macromolecules ranging in size from less than 7 nm to more than 14 nm (5), and the cholesterol content of the different species can vary 3-fold. Indeed, several lines of evidence suggest that the association between HDL-C levels and CVD status is indirect and that elevating HDL-C is not necessarily therapeutic (6)(7)(8)(9)(10)(11)(12). For example, genetic variations that associate with altered HDL-C do not strongly associate with altered CVD risk (9).…”

Section: Introductionmentioning

confidence: 99%