SEARCH:   Advanced

Blood, 15 October 2008, Vol. 112, No. 8, pp. 3205-3216. Prepublished online as a Blood First Edition Paper on July 24, 2008; DOI 10.1182/blood-2008-03-143479. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-03-143479v1 112/8/3205    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, C. Articles by Yao, Q. Search for Related Content PubMed PubMed Citation Articles by Chen, C. Articles by Yao, Q. Related Collections Hemostasis, Thrombosis, and Vascular Biology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells Changyi Chen1, Hong Chai1, Xinwen Wang1, Jun Jiang1, Md Saha Jamaluddin1, Dan Liao1, Yuqing Zhang1, Hao Wang1, Uddalak Bharadwaj1, Sheng Zhang1, Min Li1, Peter Lin1, and Qizhi Yao1 1 Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX The purpose of this study was to determine the effects and mechanisms of sCD40L on endothelial dysfunction in both human coronary artery endothelial cells (HCAECs) and porcine coronary artery rings. HCAECs treated with sCD40L showed significant reductions of endothelial nitric oxide synthase (eNOS) mRNA and protein levels, eNOS mRNA stability, eNOS enzyme activity, and cellular NO levels, whereas superoxide anion (O2–) production was significantly increased. sCD40L enhanced eNOS mRNA 3'UTR binding to cytoplasmic molecules and induced a unique expression pattern of 95 microRNAs. sCD40L significantly decreased mitochondrial membrane potential, and catalase and SOD activities, whereas it increased NADPH oxidase (NOX) activity. sCD40L increased phosphorylation of MAPKs p38 and ERK1/2 as well as IB and enhanced NF-B nuclear translocation. In porcine coronary arteries, sCD40L significantly decreased endothelium-dependent vasorelaxation and eNOS mRNA levels, whereas it increased O2– levels. Antioxidant seleno-L-methionine; chemical inhibitors of p38, ERK1/2, and mitochondrial complex II; as well as dominant negative mutant forms of IB and NOX4 effectively blocked sCD40L-induced eNOS down-regulation in HCAECs. Thus, sCD40L reduces eNOS levels, whereas it increases oxidative stress through the unique molecular mechanisms involving eNOS mRNA stability, 3'UTR-binding molecules, microRNAs, mitochondrial function, ROS-related enzymes, p38, ERK1/2, and NF-B signal pathways in endothelial cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Y. Stokes, L. Calahan, C. M. Hamric, J. M. Russell, and D. N. Granger CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H689 - H697. [Abstract] [Full Text] [PDF] X. Wang, H. Chai, Z. Wang, P. H. Lin, Q. Yao, and C. Chen Serum amyloid A induces endothelial dysfunction in porcine coronary arteries and human coronary artery endothelial cells Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2399 - H2408. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020