This Article Full Text Full Text (PDF) 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Qian, Z. Articles by Lowenstein, C. J. Search for Related Content PubMed PubMed Citation Articles by Qian, Z. Articles by Lowenstein, C. J. Related Collections Other arteriosclerosis Genetically altered mice Transplantation Endothelium/vascular type/nitric oxide Mechanism of atherosclerosis/growth factors

(Circulation. 2001;104:2369.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Inducible Nitric Oxide Synthase Inhibition of Weibel-Palade Body Release in Cardiac Transplant Rejection

Zhiping Qian, MD; Ramona Gelzer-Bell, MD; Shui-xiang Yang, MD PhD; Wangsen Cao, MD PhD; Tomokazu Ohnishi, PhD; Barbara A. Wasowska, PhD; Ralph H. Hruban, MD; E. Rene Rodriguez, MD; William M. Baldwin, III, MD PhD; Charles J. Lowenstein, MD

From the Division of Cardiology, Department of Medicine (R.G.-B., W.C., T.O., C.J.L.), and the Department of Pathology (Z.Q., S.Y., B.A.W., R.H.H., E.R.R., W.M.B., C.J.L.), Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Charles J. Lowenstein, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 950 Ross Bldg, 720 Rutland Ave, Baltimore, MD 21205. E-mail clowenst{at}jhmi.edu

Background— Inducible nitric oxide synthase (iNOS, or NOS2) reduces the severity of accelerated graft arteriosclerosis (AGA) in transplanted organs, although the precise mechanism is unclear.

Methods and Results— We transplanted wild-type murine hearts into either wild-type or NOS2-null recipient mice; we then measured cardiac allograft survival and analyzed tissue sections by immunohistochemistry. We have confirmed that NOS2 increases cardiac allograft survival. We now show that there is less inflammation of cardiac allografts in wild-type hosts than in NOS2-null hosts. Furthermore, staining for von Willebrand factor reveals that the presence of NOS2 is correlated with the presence of Weibel-Palade bodies inside endothelial cells, whereas the absence of NOS2 is correlated with the release of Weibel-Palade bodies.

Conclusions— Weibel-Palade bodies contain mediators that promote thrombosis and inflammation. Therefore, nitric oxide (NO) may stabilize the vessel wall and prevent endothelial activation in part by inhibiting the release of the contents of Weibel-Palade bodies. Prevention of Weibel-Palade body release might be a mechanism by which NO protects the vessel wall from inflammatory disorders such as atherosclerosis or graft arteriosclerosis.

Key Words: selectins • rejection • transplantation • grafting • arteriosclerosis

This article has been cited by other articles:

				S. Schmidt, T. H. Westhoff, P. Krauser, W. Zidek, and M. van der Giet The uraemic toxin phenylacetic acid increases the formation of reactive oxygen species in vascular smooth muscle cells Nephrol. Dial. Transplant., January 1, 2008; 23(1): 65 - 71. [Abstract] [Full Text] [PDF]

				Y. Kanno, T. Into, C. J. Lowenstein, and K. Matsushita Nitric oxide regulates vascular calcification by interfering with TGF-{beta} signalling Cardiovasc Res, January 1, 2008; 77(1): 221 - 230. [Abstract] [Full Text] [PDF]

				M. Ferlito, K. Irani, N. Faraday, and C. J. Lowenstein Nitric oxide inhibits exocytosis of cytolytic granules from lymphokine-activated killer cells PNAS, August 1, 2006; 103(31): 11689 - 11694. [Abstract] [Full Text] [PDF]

				C.-Y. Wei, K.-C. Huang, Y.-H. Chou, P.-F. Hsieh, K.-H. Lin, and W.-W. Lin The Role of Rho-Associated Kinase in Differential Regulation by Statins of Interleukin-1beta- and Lipopolysaccharide-Mediated Nuclear Factor {kappa}B Activation and Inducible Nitric-Oxide Synthase Gene Expression in Vascular Smooth Muscle Cells Mol. Pharmacol., March 1, 2006; 69(3): 960 - 967. [Abstract] [Full Text] [PDF]

				M. Yamakuchi, J. J.M. Greer, S. J. Cameron, K. Matsushita, C. N. Morrell, K. Talbot-Fox, W. M. Baldwin III, D. J. Lefer, and C. J. Lowenstein HMG-CoA Reductase Inhibitors Inhibit Endothelial Exocytosis and Decrease Myocardial Infarct Size Circ. Res., June 10, 2005; 96(11): 1185 - 1192. [Abstract] [Full Text] [PDF]

				K. Matsushita, M. Yamakuchi, C. N. Morrell, M. Ozaki, B. O'Rourke, K. Irani, and C. J. Lowenstein Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis Blood, January 1, 2005; 105(1): 207 - 214. [Abstract] [Full Text] [PDF]

				N. Goren, J. Cuenca, P. Martin-Sanz, and L. Bosca Attenuation of NF-{kappa}B signalling in rat cardiomyocytes at birth restricts the induction of inflammatory genes Cardiovasc Res, November 1, 2004; 64(2): 289 - 297. [Abstract] [Full Text] [PDF]

				R. Bhatia, K. Matsushita, M. Yamakuchi, C. N. Morrell, W. Cao, and C. J. Lowenstein Ceramide Triggers Weibel-Palade Body Exocytosis Circ. Res., August 6, 2004; 95(3): 319 - 324. [Abstract] [Full Text] [PDF]

				K. Matsushita, C. N. Morrell, and C. J. Lowenstein Sphingosine 1-phosphate activates Weibel-Palade body exocytosis PNAS, August 3, 2004; 101(31): 11483 - 11487. [Abstract] [Full Text] [PDF]

				G. Pilon, P. Dallaire, and A. Marette Inhibition of Inducible Nitric-oxide Synthase by Activators of AMP-activated Protein Kinase: A NEW MECHANISM OF ACTION OF INSULIN-SENSITIZING DRUGS J. Biol. Chem., May 14, 2004; 279(20): 20767 - 20774. [Abstract] [Full Text] [PDF]

				S. C. Stoica, D. K. Satchithananda, C. Atkinson, S. Charman, M. Goddard, and S. R. Large Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 932 - 939. [Abstract] [Full Text] [PDF]