Uremia alters HDL composition and cholesterol efflux capacity

Functional impairment of HDL may contribute to the excess cardiovascular mortality experienced by patients with renal disease, but the effect of advanced renal disease on the composition and function of HDL is not well understood.

Mass spectrometry and biochemical analyses were used to study alterations in the proteome and lipid composition of HDL isolated from patients on maintenance hemodialysis.

We identified a significant increase in the amount of acute-phase protein serum amyloid A1, albumin, lipoprotein-associated phospholipase A₂, and apoC-III composing uremic HDL. Furthermore, uremic HDL contained reduced phospholipids and increased triglycerides and lysophospholipids. With regard to function, these changes impaired the ability of uremic HDL to promote cholesterol efflux from macrophages.

In summary, the altered composition of HDL in renal disease seems to inhibit the cardioprotective properties of HDL. Assessing HDL composition and function in renal disease may help to identify patients at increased risk for cardiovascular disease.

This work was supported by the Austrian Science Fund FWF (grants P21004-B02 and P22976-B18).

Affiliations

1. Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010, Graz, Austria

   • Michael Holzer
   • , Dalia El-Gamal
   • , Veronika Binder
   • , Ákos Heinemann
   •  & Gunther Marsche

2. Proteomics Core Facility, Centre for Medical Research, Medical University of Graz, 8036, Graz, Austria

   • Ruth Birner-Grünberger

3. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036, Graz, Austria

   • Tatjana Stojaković

4. Department of Obstetrics and Gynecology, Medical University of Graz, 8036, Graz, Austria

   • Christian Wadsack

Corresponding author

Correspondence to Gunther Marsche.

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