Abstract | OBJECTIVES: BACKGROUND: METHODS: Cellular cholesterol efflux and inflammatory response were assessed in macrophages exposed to HDL of patients with ESRD-HD or controls. RESULTS: HDL from patients with ESRD-HD was dramatically less effective than normal HDL in accepting cholesterol from macrophages (median 6.9%; interquartile range [IQR]: 1.4% to 10.2%) versus control (median 14.9%; IQR: 9.8% to 17.8%; p < 0.001). The profound efflux impairment was also seen in patients with ESRD-HD and diabetes compared with patients with diabetes without renal disease (median 8.1%; IQR: 3.3% to 12.9%) versus control (median 13.6%; IQR: 11.0% to 15.9%; p = 0.009). In vitro activation of cellular cholesterol transporters increased cholesterol efflux to both normal and uremic HDL. HDL of patients with ESRD-HD had reduced antichemotactic ability and increased macrophage cytokine response ( tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). HDL of patients with ESRD-HD on statin therapy had reduced inflammatory response while maintaining impaired cholesterol acceptor function. Interestingly, impaired HDL-mediated efflux did not correlate with circulating C-reactive protein levels or cellular inflammatory response. CONCLUSIONS: These findings suggest that abnormal HDL capacity to mediate cholesterol efflux is a key driver of excess CVD in patients on chronic hemodialysis and may explain why statins have limited effect to decrease CV events. The findings also suggest cellular cholesterol transporters as potential therapeutic targets to decrease CV risk in this population.
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Authors | Suguru Yamamoto, Patricia G Yancey, T Alp Ikizler, W Gray Jerome, Ryohei Kaseda, Brian Cox, Aihua Bian, Ayumi Shintani, Agnes B Fogo, Macrae F Linton, Sergio Fazio, Valentina Kon |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 60
Issue 23
Pg. 2372-9
(Dec 11 2012)
ISSN: 1558-3597 [Electronic] United States |
PMID | 23141484
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Atherosclerosis
(blood, etiology)
- Dyslipidemias
(blood, complications)
- Female
- Follow-Up Studies
- Humans
- Kidney Failure, Chronic
(blood, therapy)
- Lipoproteins, HDL
(blood)
- Male
- Middle Aged
- Renal Dialysis
(adverse effects, methods)
- Time Factors
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