| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Divisions of 1Cardiothoracic Surgery and 2Pediatric Cardiology, Medical University of South Carolina, Charleston, South Carolina 29425
Submitted 15 May 2003 ; accepted in final form 14 November 2003
Discrete myocardial lesions created through the delivery of radiofrequency (RF) energy can expand; however, the mechanisms have not been established. Matrix metalloproteinases (MMPs) play an important role in myocardial remodeling, and MMP activity can be regulated by the tissue inhibitors of the metalloproteinases (TIMPs). This study examined the role of TIMP-1 in postinjury myocardial remodeling. Lesions were created on the left ventricular (LV) epicardium of wild-type (WT, 8–12 wk, 129SVE) and age-matched TIMP-1 gene-deficient (timp-1–/–) mice through the delivery of RF current (80°C, 30 s). Heart mass, LV scar volumes, and collagen content were measured at 1 h and 3, 7, and 28 days postinjury (n = 10 each). Age-matched, nonablated mice were used as reference controls (n = 5). Heart mass indexed to tibial length increased in WT and timp-1–/– mice but was greater in the timp-1–/– mice by 7 days. Scar volumes increased in a time-dependent manner in both groups but were higher in the timp-1–/– mice than the WT mice at 7 days (1.48 ± 0.09 vs. 1.20 ± 0.11 mm3·mg–1·mm, P < 0.05) and remained higher at 28 days. In the remote myocardium, wall thickness was greater and relative collagen content was lower in the timp-1–/– mice at 28 days postinjury. Discrete myocardial RF lesions expand in a time-dependent manner associated with myocyte hypertrophy remote to the scar. Moreover, postinjury myocardial remodeling was more extensive with TIMP-1 gene deletion. Thus TIMP-1 either directly or through modulation of MMP activity may regulate myocardial remodeling following infliction of a discrete injury.
myocardial remodeling; tissue inhibitors of metalloproteinases-1; mouse
This article has been cited by other articles:
|
|
 |
|
  S. K. Mani, S. Balasubramanian, J. A. Zavadzkas, L. B. Jeffords, W. T. Rivers, M. R. Zile, R. Mukherjee, F. G. Spinale, and D. Kuppuswamy Calpain inhibition preserves myocardial structure and function following myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1744 - H1751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Janssens and H. R. Lijnen What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models? Cardiovasc Res, February 15, 2006; 69(3): 585 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Vanhoutte, M. Schellings, Y. Pinto, and S. Heymans Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial window Cardiovasc Res, February 15, 2006; 69(3): 604 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Sukhova, B. Wang, P. Libby, J.-H. Pan, Y. Zhang, A. Grubb, K. Fang, H. A. Chapman, and G.-P. Shi Cystatin C Deficiency Increases Elastic Lamina Degradation and Aortic Dilatation in Apolipoprotein E-Null Mice Circ. Res., February 18, 2005; 96(3): 368 - 375. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
