Results Competition of 5 A peptide and known CD 36 ligands with Alexa-Fluor 488 oxLDL in CD 36-overexpressing HeLa cells

Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein AI-mimetic peptide 5A antagonizes CD36 in vitro. To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild type to CD36 knockout mice and wild type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreases renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for To whom correspondence should be addressed: Robert A. Star, M.D., Division of Kidney, Urologic, and Hematologic Diseases, National Institutes of Health, NIDDK 6707 Democracy Blvd., Room 625; Bethesda, MD 20892; Phone: (301) 496-6325; starr@niddk.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The authors declare that there are no conflicts of interest. HHS Public Access Author manuscript Kidney Int. Author manuscript; available in PMC 2017 April 01. Published in final edited form as: Kidney Int. 2016 April ; 89(4): 809–822. doi:10.1016/j.kint.2015.12.043. A uhor M anscript