Authors

Yi Liu, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Yanzhuo Ma, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Rutao Wang, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Chenhai Xia, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Rongqing Zhang, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Kun Lian, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Ronghua Luan, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Lu Sun, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Lu Yang, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Wayne B Lau, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Haichang Wang, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China
Ling Tao, Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changle West Road, Xi'an 710032, China

Document Type

Article

Publication Date

10-1-2011

Comments

This article has been peer reviewed and is published in Antioxidants & Redox Signaling 2011 Oct 1; 15(7):1769-78. The published version is available at DOI: 10.1089/ars.2010.3764. ©Mary Ann Liebert, Inc

Abstract

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population.

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