title: Myocardial remodeling after discrete radiofrequency injury: effects of tissue inhibitor of matrix metalloproteinase-1 gene deletion.
abstract: 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 degrees 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 mm(3).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.
authors: Division of Cardiothoracic Surgery, University of South Carolina, Charleston, SC 29425, USA. mukherr@musc.edu
authors: Rupak
authors: R
authors: Mukherjee
authors: Andrea M
authors: AM
authors: Parkhurst
authors: Joseph T
authors: JT
authors: Mingoia
authors: Sarah E
authors: SE
authors: Sweterlitsch
authors: Jennifer S
authors: JS
authors: Leiser
authors: G Patricia
authors: GP
authors: Escobar
authors: Francis G
authors: FG
authors: Spinale
authors: J Philip
authors: JP
authors: Saul
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D017353:Gene Deletion; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D011846:Radio Waves; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics* / Q000502:physiology*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020781:Matrix Metalloproteinase 1