A role for decorin in the remodeling of myocardial infarction.
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.
Weis
Sara M
SM
Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093, USA. sweis@ucsd.edu
Zimmerman
Scott D
SD
Shah
Maithili
M
Covell
James W
JW
Omens
Jeffrey H
JH
Ross
John
J
Dalton
Nancy
N
Jones
Ying
Y
Reed
Charles C
CC
Iozzo
Renato V
RV
McCulloch
Andrew D
AD
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
C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D003094:Collagen