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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 6, 2008 Accepted July 14, 2008 Soluble CD40 ligand induces endothelial dysfunction in human and porcine coronary artery endothelial cells Changyi Chen*, Hong Chai, Xinwen Wang, Jun Jiang, Md. Saha Jamaluddin, Dan Liao, Yuqing Zhang, Hao Wang, Uddalak Bharadwaj, Sheng Zhang, Min Li, Peter Lin, and Qizhi Yao Vascular Surgery, Baylor College of Medicine, Houston, Texas, United States * Corresponding author; email: jchen{at}bcm.tmc.edu. 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, while 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, while 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, while 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 downregulation in HCAECs. Thus, sCD40L reduces eNOS levels, while 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: C. Antoniades, C. Bakogiannis, D. Tousoulis, A. S. Antonopoulos, and C. Stefanadis The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J. Am. Coll. Cardiol., August 18, 2009; 54(8): 669 - 677. [Abstract] [Full Text] [PDF] 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