Unraveling the complexities of the HDL lipidome

Kontush, Anatol; Lhomme, Marie; Chapman, M. John

doi:10.1194/jlr.r036095

Cited by 310 publications

(270 citation statements)

References 143 publications

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“…Some of these assays may be amenable to routine diagnostic testing and relate to HDL function, and hence CVD risk. The best example of this is the use of nuclear magnetic resonance (NMR) spectroscopy for measuring HDL particle number, which has been shown in several large studies to be superior to HDL-C in predicting future cardiovascular events (4,183,184 ). NMR can also be used to quantify specific HDL subfractions, such as apoB-containing lipoproteins, as well as LDL and HDL particle size and distribution, which may also be predictive of increased mortality in a wide range of disease states (185)(186)(187)(188)(189)(190).…”

Section: Hdl Assays Based On Physical Propertiesmentioning

confidence: 99%

The Changing Face of HDL and the Best Way to Measure It

Karathanasis¹,

Freeman

Gordon

et al. 2017

Clinical Chemistry

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BACKGROUND: HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests. CONTENT:This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters.

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Section: Hdl Assays Based On Physical Propertiesmentioning

confidence: 99%

The Changing Face of HDL and the Best Way to Measure It

Karathanasis¹,

Freeman

Gordon

et al. 2017

Clinical Chemistry

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“…219 The phospholipid content and composition have a strong effect on the size, shape, fluidity, and surface charge of HDLs. 28 Their contribution to the functionality of HDLs has been tested experimentally by reconstituting artificial HDL particles with defined phosphatidylcholine species at different concentrations. Increased concentrations of phosphatidylcholine increase the ability of HDLs to induce SR-BI-mediated cholesterol efflux.…”

Section: Post-translational Modifications Of Proteinsmentioning

confidence: 99%

High-Density Lipoproteins

Annema

Eckardstein

2013

Circ J

142

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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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“…19 Hence, it is assumed that the cardioprotective effects of HDL are largely based on its ability to remove cholesterol from macrophages, which represents the first and crucial step of reverse cholesterol transport. 20 In recent years, it has become evident that the atheroprotective, anti-inflammatory, and antioxidative effects of HDL are critically dependent on its protein cargo [21][22][23][24] because HDLassociated proteins were found to be involved in many biologic functions apart from lipid metabolism, such as regulation of inflammation and immune responsiveness. 15 We and others have shown that qualitative alterations of HDL in CKD and ESRD result in dysfunctional properties, transforming HDL from a protective to a deleterious particle.…”

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confidence: 99%

Restoration of Renal Function Does Not Correct Impairment of Uremic HDL Properties

Kopecky¹,

Haidinger²,

Birner-Grünberger³

et al. 2015

Journal of the American Society of Nephrology

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Cardiovascular disease remains the leading cause of death in renal transplant recipients, but the underlying causative mechanisms for this important problem remain elusive. Recent work has indicated that qualitative alterations of HDL affect its functional and compositional properties in ESRD. Here, we systematically analyzed HDL from stable renal transplant recipients, according to graft function, and from patients with ESRD to determine whether structural and functional properties of HDL remain dysfunctional after renal transplantation. Cholesterol acceptor capacity and antioxidative activity, representing two key cardioprotective mechanisms of HDL, were profoundly suppressed in kidney transplant recipients independent of graft function and were comparable with levels in patients with ESRD. Using a mass spectroscopy approach, we identified specific remodeling of transplant HDL with highly enriched proteins, including a-1 microglobulin/bikunin precursor, pigment epithelium-derived factor, surfactant protein B, and serum amyloid A. In conclusion, this study demonstrates that HDL from kidney recipients is uniquely altered at the molecular and functional levels, indicating a direct pathologic role of HDL that could contribute to the substantial cardiovascular risk in the transplant population.

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Unraveling the complexities of the HDL lipidome

Cited by 310 publications

References 143 publications

The Changing Face of HDL and the Best Way to Measure It

The Changing Face of HDL and the Best Way to Measure It

High-Density Lipoproteins

Restoration of Renal Function Does Not Correct Impairment of Uremic HDL Properties

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