ApoA-1 Mimetic Peptide Reverses Uremia-Induced Upregulation of Pro-Atherogenic Pathways in the Aorta

作者：Vaziri Nosratola D^*; Bai Yongli; Yuan Jun; Said Hannah L; Sigala Whitney; Ni Zhemin

来源：American Journal of Nephrology, 2010, 32(3): 201-211.

DOI：10.1159/000316479

• Atherosclerosis
• Dyslipidemia
• High-density lipoprotein cholesterol
• Chronic kidney disease
• End-stage renal disease
• Cardiovascular disease
• Inflammation
• Oxidative stress
• Reverse cholesterol transport
• Anti-inflammatory agents

Background: Chronic kidney disease (CKD) results in accelerated atherosclerosis and cardiovascular disease. This is primarily mediated by oxidative stress, inflammation and dys-lipidemia. 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/antiinflammatory 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. Methods: 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. Results: 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, myelo-peroxidase and iNOS, NF kappa B activation and nitrotyrosine accumulation in the thoracic aorta. L4F administration reversed or attenuated these abnormalities without altering renal function or plasma lipids. Conclusions: CKD leads to lipid accumulation and upregulation of pro-atherogenic pathways in the artery wall. These abnormalities are attenuated by ApoA-1 mimetic peptide, pointing to its protective effect in CKD. Future studies are needed to explore the effect of these peptides in CKD patients.

• 出版日期2010