Published online before print December 31, 2001, doi: 10.1161/hc0602.103639
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:720.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Altered Expression of ADAMs (A Disintegrin And Metalloproteinase) in Fibrillating Human Atria
From the Institute of Experimental Internal Medicine (M.A., U.L., C.W., A.S., S.A.), Institute of Pathology (C.R.), Department of Cardiovascular Surgery (C.H.), and Division of Cardiology (K.N., H.U.K., A.G.), University Hospital Magdeburg, Germany.
Correspondence to Andreas Goette, MD, Department of Internal Medicine, Division of Cardiology, University Hospital Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. E-mail andreas.goette{at}medizin.uni-magdeburg.de
Background— ADAMs (A Disintegrin And Metalloproteinase) are ectoproteases that have recently been reported to be expressed in cardiac tissue. Although they are known to regulate cell-cell and cell-matrix interactions, their pathophysiological role in various cardiac diseases is unclear. The purpose of the present study was to determine whether structural remodeling of the atria during atrial fibrillation (AF) is associated with altered ADAM expression.
Methods and Results— Atrial tissue samples of 30 patients undergoing open-heart surgery were examined. Fifteen patients had persistent AF (
6 months), and the remaining 15 patients had no history of AF. ADAM9, ADAM10, and ADAM15 expression was analyzed quantitatively at the mRNA and protein levels. ADAM expression was localized by immunohistochemistry. ADAM expression was correlated with amounts of integrins ß1 and ß3. The amount of ADAM10 protein more than doubled during AF (82±15 versus 36±8 U; P<0.01). Amounts of ADAM15 protein (102±12 versus 40±6 U; P<0.01) and mRNA (24.0±5.6 versus 10.5±2.5 U; P<0.05) increased significantly during AF compared with sinus rhythm. ADAM9 protein was not detected in any sample. ADAM/integrin ratios showed an increase of 4- to 6-fold (P<0.05) in patients with AF who had significantly dilated atria (4.94±0.6 versus 4.3±0.7 cm; P<0.05). ADAM/integrin ratios correlated with atrial diameter.
Conclusions— AF is associated with an increase in the expression of ADAM10 and ADAM15. Enhanced ADAM-dependent disintegrin and metalloproteinase activity may be a molecular mechanism that contributes to the dilation of fibrillating human atria.
Key Words: metalloproteinases • fibrillation • pathology • remodeling
This article has been cited by other articles:
 |
|
 |
|
  A. M. Manso, L. Elsherif, S.-M. Kang, and R. S. Ross Integrins, membrane-type matrix metalloproteinases and ADAMs: Potential implications for cardiac remodeling Cardiovasc Res, February 15, 2006; 69(3): 574 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W.M. Fedak, C. S. Moravec, P. M. McCarthy, S. M. Altamentova, A. P. Wong, M. Skrtic, S. Verma, R. D. Weisel, and R.-K. Li Altered Expression of Disintegrin Metalloproteinases and Their Inhibitor in Human Dilated Cardiomyopathy Circulation, January 17, 2006; 113(2): 238 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Anne, R. Willems, T. Roskams, P. Sergeant, P. Herijgers, P. Holemans, H. Ector, and H. Heidbuchel Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation Cardiovasc Res, September 1, 2005; 67(4): 655 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Lalu, E. Pasini, C. J. Schulze, M. Ferrari-Vivaldi, G. Ferrari-Vivaldi, T. Bachetti, and R. Schulz Ischaemia-reperfusion injury activates matrix metalloproteinases in the human heart Eur. Heart J., January 1, 2005; 26(1): 27 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hanna, S. Cardin, T.-K. Leung, and S. Nattel Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure Cardiovasc Res, August 1, 2004; 63(2): 236 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakano, S. Niida, K. Dote, S. Takenaka, H. Hirao, F. Miura, M. Ishida, T. Shingu, T. Sueda, M. Yoshizumi, et al. Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation J. Am. Coll. Cardiol., March 3, 2004; 43(5): 818 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Hoit Matrix metalloproteinases and atrial structural remodeling J. Am. Coll. Cardiol., July 16, 2003; 42(2): 345 - 347. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Marin, V. Roldan, V. Climent, A. Garcia, P. Marco, and G. Y.H. Lip Is Thrombogenesis in Atrial Fibrillation Related to Matrix Metalloproteinase-1 and Its Inhibitor, TIMP-1? Stroke, May 1, 2003; 34(5): 1181 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Hintz, A. J. Rassias, K. Wardwell, M. L. Moss, P. M. Morganelli, P. A. Pioli, A. L. Givan, P. K. Wallace, M. P. Yeager, and P. M. Guyre Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163 J. Leukoc. Biol., October 1, 2002; 72(4): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shizukuda and P. M. Buttrick Oxygen free radicals and heart failure: new insight into an old question Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L237 - L238. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goette, M. Arndt, C. Rocken, T. Staack, R. Bechtloff, D. Reinhold, C. Huth, S. Ansorge, H. U. Klein, and U. Lendeckel Calpains and cytokines in fibrillating human atria Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H264 - H272. [Abstract] [Full Text] [PDF]
|
|