Document Detail

Cardiac Restricted Overexpression Or Deletion Of Tissue Inhibitor Of Matrix Metalloproteinase-4.
MedLine Citation:
PMID:  24993046     Owner:  NLM     Status:  Publisher    
Historically, the tissue inhibitors of matrix metalloproteinases were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice with TIMP-4OE (n=38), TIMP-4KO (n=24), as well as age/strain matched wild type (WT, n = 25), whereby indices of LV remodeling and function, such as LV mass and ejection fraction (LVEF), were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was approximately 25% lower in the TIMP-4KO group (p<0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (47±2% and 45±3%, respectively) but was higher with TIMP-4OE (57±2%, p<0.05). With LVPO, LV myocardial collagen expression (type I,III) increased by 3-fold in all groups (p<0.05), but surprisingly this response was most robust in the TIMP-4KO group.
William M Yarbrough; Catalin F Baicu; Rupak Mukherjee; An O Van Laer; William T Rivers; Richard A McKinney; Corey B Prescott; Robert E Stroud; Parker D Freels; Kia N Zellars; Michael R Zile; Francis G Spinale
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-3
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
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