Increased Plasma Chymase Concentration and Mast Cell Chymase Expression in Venous Neointimal Lesions of Patients with CKD and ESRD

• Type of Material: Article
• Authors: Haimanot Wasse, Emory University; Rong Huang, Emory University; Deborah E. Martinson, Emory University; Juan Angel Rivera, Emory University; Qi Long, Emory University; William M. McKinnon, Emory University; Nawazish Ali Naqvi, Emory University; Ahsan Husain, Emory University
• Language: English
• Date: 2011-11
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Wiley Periodicals, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/j.1525-139X.2011.00921.x/abstract;jsessionid=ECC43F267FFB9F1A31E0F3A93FCA5E5D.d03t01?systemMessage=Wiley+Online+Library+will+be+disrupted+on+7+July+from+10%3A00-12%3A00+BST+%2805%3A00-07%3A00+EDT%29+for+essential+maintenance
• Title of Journal or Parent Work: Seminars in Dialysis
• ISSN: 0894-0959
• Volume: 24
• Issue: 6
• Start Page: 688
• End Page: 693
• Grant/Funding Information: This study was supported by an NIH K23 Award (H.W) and a PHS Grant (UL1 RR02008, KL2 RR025009 or TL1 RR025010) from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources.
• Research Categories: Biology, Bioinformatics; Health Sciences, Medicine and Surgery

Abstract

The underlying inflammatory component of chronic kidney disease may predispose blood vessels to intimal hyperplasia (IH), which is the primary cause of dialysis access failure. We hypothesize that vascular pathology andmarkers of IH formation are antecedent to arteriovenous (AV) fistula creation. Blood, cephalic, and basilic vein segments were collected from predialysis chronic kidney disease (CKD) patients with no previous AV access and patients with end-stage renal disease (ESRD). Immunohistochemistry was performed with antibodies against mast cell chymase, transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6), which cause IH. Plasma chymase was measured by ELISA. IH was present in 91% of CKD and 75% of ESRD vein segments. Chymase was abundant in vessels with IH, with the greatest expression in intima and medial layers, and virtually absent in the controls. Chymase colocalized with TGF-β1 and IL-6. Plasma chymase concentration was elevated up to 33-fold in patients with CKD versus controls and was associated with increased chymase in vessels with IH. We show that chymase expression in vessels with IH corresponds with plasma chymase concentrations. As chymase inhibition attenuates IH in animal models, and we find chymase is highly expressed in IH lesions of patients with CKD and ESRD, we speculate that chymase inhibition could have therapeutic value in humans.