title: A role for decorin in the remodeling of myocardial infarction.
abstract: Because the small leucine-rich proteoglycan decorin has been implicated in regulation of collagen fibrillogenesis leading to proper extracellular matrix assembly, we hypothesized it could play a key role in cardiac fibrosis following myocardial infarction. In this study we ligated the left anterior descending coronary artery in wildtype and decorin-null mice to produce large infarcts in the anterior wall of the left ventricle. At early stages post-coronary occlusion the myocardial infarction size did not appreciably differ between the two genotypes. However, we found a wider distribution of collagen fibril sizes with less organization and loose packing in mature scar from decorin-null mice. Thus, we tested the hypothesis that these abnormal collagen fibrils would adversely affect post-infarction mechanics and ventricular remodeling. Indeed, scar size, right ventricular remote hypertrophy, and left ventricular dilatation were greater in decorin-null animals compared with wildtype littermates 14 days after acute myocardial infarction. Echocardiography revealed depressed left ventricular systolic function between 4 and 8 weeks post-ischemia in the decorin-null animals. These changes indicate that decorin is required for the proper fibrotic evolution of myocardial infarctions, and that its absence leads to abnormal scar tissue formation. This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function.
authors.affiliation: Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093, USA. sweis@ucsd.edu
authors.forename: Sara M
authors.initials: SM
authors.lastname: Weis
authors.forename: Scott D
authors.initials: SD
authors.lastname: Zimmerman
authors.forename: Maithili
authors.initials: M
authors.lastname: Shah
authors.forename: James W
authors.initials: JW
authors.lastname: Covell
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
authors.forename: John
authors.initials: J
authors.lastname: Ross
authors.forename: Nancy
authors.initials: N
authors.lastname: Dalton
authors.forename: Ying
authors.initials: Y
authors.lastname: Jones
authors.forename: Charles C
authors.initials: CC
authors.lastname: Reed
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D009929:Organ Size / Q000235:genetics; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D003094:Collagen