title: Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation.
abstract: 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 A-I-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 decreased renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression.
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Ana Carolina P
authors.initials: AC
authors.lastname: Souza
authors.affiliation: Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Bocharov
authors.affiliation: Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Baranova
authors.affiliation: Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA.
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Vishnyakova
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Yuning G
authors.initials: YG
authors.lastname: Huang
authors.affiliation: Biostatistics Program, NIDDK, NIH, Bethesda, Maryland, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Wilkins
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Street
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alvarez-Prats
authors.affiliation: ISIS Pharmaceuticals, Carlsbad, California, USA.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Mullick
authors.affiliation: Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA; Office of the Director, NIH, Bethesda, Maryland, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Patterson
authors.affiliation: Lipoprotein Metabolism Section, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA; Division of Diabetes, Endocrinology, and Metabolic Diseases, NIDDK, NIH, Bethesda, Maryland, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Eggerman
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Peter S T
authors.initials: PS
authors.lastname: Yuen
authors.affiliation: Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA. Electronic address: starr@niddk.nih.gov.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure; D018955:CD36 Antigens / Q000037:antagonists & inhibitors*; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009392:Nephrectomy; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000517:prevention & control*; D014517:Ureteral Obstruction / Q000276:immunology / Q000473:pathology
chemical_list: C000613704:5A peptide; D018955:CD36 Antigens; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D005456:Fluorescent Dyes; C587672:IL1B protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D010455:Peptides; C577686:interleukin-6, mouse; D000804:Angiotensin II
keywords: albuminuria; glomerulosclerosis; inflammasome; inflammation; interstitial fibrosis; remnant kidney model; telemetry