ApoA-1 mimetic peptide reverses uremia-induced upregulation of pro-atherogenic pathways in the aorta

American Journal of Nephrology
Nosratola D VaziriZhemin Ni

Abstract

Chronic kidney disease (CKD) results in accelerated atherosclerosis and cardiovascular disease. This is primarily mediated by oxidative stress, inflammation and dyslipidemia. By mediating reverse cholesterol transport and exerting antioxidant/anti-inflammatory actions, high-density lipoprotein (HDL) and ApoA-1 protect against atherosclerosis. Plasma Apo-1, HDL cholesterol and HDL antioxidant/anti-inflammatory activities are reduced in CKD. ApoA-1 mimetic peptides associate with and enhance antioxidant/anti-inflammatory properties of HDL. We hypothesized that long-term administration of ApoA-1 mimetic peptide, L4F, may ameliorate inflammation and oxidative stress in the conduit arteries in experimental CKD. After 5/6 nephrectomy, rats were randomized to L4F (5 mg/kg s.c. 3 times weekly for 4 weeks) and placebo-treated groups. Sham-operated rats served as controls. The untreated CKD group exhibited marked lipid accumulation and upregulations of NAD(P)H oxidase subunits (gp91(phox), p22(phox), and p47(phox)), COX-2, 12-lipoxygenase, MCP-1, PAI-1, myeloperoxidase and iNOS, NFκB activation and nitrotyrosine accumulation in the thoracic aorta. L4F administration reversed or attenuated these abnormalities without altering renal functi...Continue Reading

Citations

Oct 10, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kyubok JinNosratola D Vaziri
Jul 16, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Martha K PastuszkaJ Andrew MacKay
Feb 27, 2017·American Journal of Nephrology·Ivano BaragettiPaolo Fiorina
Jan 19, 2017·Current Opinion in Endocrinology, Diabetes, and Obesity·Tae Ik ChangHamid Moradi
Mar 18, 2016·Vascular and Endovascular Surgery·Alex HelkinVivian Gahtan
Nov 3, 2010·Current Opinion in Lipidology·G K HovinghJohn J P Kastelein
Aug 26, 2014·Journal of the American Society of Nephrology : JASN·Laetitia DouStephane Burtey
Jan 27, 2012·Current Opinion in Endocrinology, Diabetes, and Obesity·Scott M Gordon, William S Davidson

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