Cardner, Mathias and Yalcinkaya, Mustafa and Goetze, Sandra and Luca, Edlira and Balaz, Miroslav and Hunjadi, Monika and Hartung, Johannes and Shemet, Andrej and Kraenkel, Nicolle and Radosavljevic, Silvija and Keel, Michaela and Othman, Alaa and Karsai, Gergely and Hornemann, Thorsten and Claassen, Manfred and Liebisch, Gerhard and Carreira, Erick and Ritsch, Andreas and Landmesser, Ulf and Kruetzfeldt, Jan and Wolfrum, Christian and Wollscheid, Bernd and Beerenwinkel, Niko and Rohrer, Lucia and von Eckardstein, Arnold (2020) Structure-function relationships of HDL in diabetes and coronary heart disease. JCI INSIGHT, 5 (1): e131491. ISSN , 2379-3708
Full text not available from this repository. (Request a copy)Abstract
High-density lipoproteins (HDL) contain hundreds of lipid species and proteins and exert many potentially vasoprotective and antidiabetogenic activities on cells. To resolve structure-function-disease relationships of HU, we characterized HDL of 51 healthy subjects and 98 patients with diabetes (T2DM), coronary heart disease (CHD), or both for protein and lipid composition, as well as functionality in 5 cell types. The integration of 40 clinical characteristics, 34 nuclear magnetic resonance (NMR) features, 182 proteins, 227 lipid species, and 12 functional read-outs by high-dimensional statistical modeling revealed, first, that CHD and T2DM are associated with different changes of HDL in size distribution, protein and lipid composition, and function. Second, different cellular functions of HDL are weakly correlated with each other and determined by different structural components. Cholesterol efflux capacity (CEC) was no proxy of other functions. Third, 3 potentially novel determinants of HDL function were identified and validated by the use of artificially reconstituted HDL, namely the sphingadienine-based sphingomyelin SM 42:3 and glycosylphosphatidylinositol-phospholipase D1 for the ability of HDL to inhibit starvation-induced apoptosis of human aortic endothelial cells and apolipoprotein F for the ability of HDL to promote maximal respiration of brown adipocytes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH-DENSITY-LIPOPROTEINS; CHOLESTEROL EFFLUX CAPACITY; TRANSFER INHIBITOR PROTEIN; HIGH-THROUGHPUT QUANTIFICATION; NUCLEAR-MAGNETIC-RESONANCE; MASS-SPECTROMETRY; ARTERY-DISEASE; APOA-IV; INSULIN-RESISTANCE; VARIABLE SELECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2021 10:37 |
| Last Modified: | 01 Apr 2021 10:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45339 |
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