High density lipoprotein (HDL) particles from end-stage renal disease patients are defective in promoting reverse cholesterol transport.
Atherosclerotic cardiovascular disease (CVD) represents the largest cause of mortality in end-stage renal disease (ESRD). CVD in ESRD is not explained by classical CVD risk factors such as HDL cholesterol mass levels making functional alterations of lipoproteins conceivable. HDL functions in atheroprotection by promoting reverse cholesterol transport (RCT), comprising cholesterol efflux from macrophage foam cells, uptake into hepatocytes and final excretion into the feces. ESRD-HDL (n = 15) were compared to healthy control HDL (n = 15) for their capacity to promote in vitro (i) cholesterol efflux from THP-1 macrophage foam cells and (ii) SR-BI-mediated selective uptake into ldla[SR-BI] cells as well as (iii) in vivo RCT. Compared with HDL from controls, ESRD-HDL displayed a significant reduction in mediating cholesterol efflux (p < 0.001) and SR-BI-mediated selective uptake (p < 0.01), two key steps in RCT. Consistently, also the in vivo capacity of ESRD-HDL to promote RCT when infused into wild-type mice was significantly impaired (p < 0.01). In vitro oxidation of HDL from healthy controls with hypochloric acid was able to fully mimic the impaired biological activities of ESRD-HDL. In conclusion, we demonstrate that HDL from ESRD patients is dysfunctional in key steps as well as overall RCT, likely due to oxidative modification.
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Josephine L C
JL
Anderson
INSERM UMR866 Lipides, Nutrition, Cancer; Faculté de Médecine, Dijon, France.
Thomas
T
Gautier
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Niels
N
Nijstad
Medizinische Klinik IV - Nephrology, Charite - Campus Benjamin Franklin, Berlin, Germany.
Markus
M
Tölle
Medizinische Klinik IV - Nephrology, Charite - Campus Benjamin Franklin, Berlin, Germany.
Mirjam
M
Schuchardt
Medizinische Klinik IV - Nephrology, Charite - Campus Benjamin Franklin, Berlin, Germany.
Markus
M
van der Giet
Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Uwe J F
UJ
Tietge
D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction
D008075:Lipoproteins, HDL; D002784:Cholesterol