Hypercholesterolemia in Progressive Renal Failure Is Associated with Changes in Hepatic Heparan Sulfate-PCSK9 Interaction

Pragyi Shrestha, Saritha Adepu, Romain R Vivès, Rana El Masri, Astrid Klooster, Fleur Kaptein, Wendy Dam, Stephan J L Bakker, Harry van Goor, Bart van de Sluis, Jacob van den Born*

*Bijbehorende auteur voor dit werk

Onderzoeksoutput: ArticleAcademicpeer review

1 Citaat (Scopus)
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Background Dyslipidemia is an important risk factor in CKD. The liver clears triglyceride-rich lipoproteins (TRL) via LDL receptor (LDLR), LDLR-related protein-1 (LRP-1), and heparan sulfate proteoglycans (HSPGs), mostly syndecan-1. HSPGs also facilitate LDLR degradation by proprotein convertase subtilisin/kexin type 9 (PCSK9). Progressive renal failure affects the structure and activity of hepatic lipoprotein receptors, PCSK9, and plasma cholesterol.

Methods Uninephrectomy- and aging-induced CKD in normotensive Wistar rats and hypertensive Munich-Wistar-Fromter (MWF) rats.

Results Compared with 22-week-old sex- and strain-matched rats, 48-week-old uninephrectomized Wistar-CKD and MWF-CKD rats showed proteinuria, increased plasma creatinine, and hypercholesterolemia (all P

Conclusions Progressive CKD induces hepatic HS elongation, leading to increased interaction with PCSK9. This might reduce hepatic lipoprotein uptake and thereby induce dyslipidemia in CKD. Therefore, PCSK9/HS may be a novel target to control dyslipidemia.

Originele taal-2English
Pagina's (van-tot)1371-1388
Aantal pagina's18
TijdschriftJournal of the American Society of Nephrology
Nummer van het tijdschrift6
StatusPublished - jun.-2021

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