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Integrative approach to study the molecular basis of post‐myocardial infarction remodeling in porcine heart
Author(s) -
Kuster Diederik,
Verhoeven Adrie,
Merkus Daphne,
Duncker Dirk
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.110.8
Subject(s) - ventricular remodeling , heart failure , myocardial infarction , ventricle , transcription factor , gene expression , microarray analysis techniques , microarray , in vivo , medicine , biology , cardiology , microbiology and biotechnology , bioinformatics , gene , genetics
After myocardial infarction (MI), the left ventricle (LV) undergoes remodelling in an attempt to maintain cardiac performance. Despite the apparent appropriateness, LV remodeling is an independent risk factor for heart failure. Although much is known about the role of individual proteins in cardiac remodeling, an integrative unbiased approach has been lacking, especially in large animal models, such as the pig. Therefore, we studied gene expression with microarray and transcription factor (TF) activity with Protein/DNA array and linked these to in vivo measurements of LV remodeling and function in pigs, by using network analysis. Three weeks after MI, LV remodeling and dysfunction as well as blunting of the β‐adrenergic response were noted in vivo . At gene expression level, matrix metalloproteinases were upregulated and the β‐adrenergic/cAMP signaling was disturbed. Network analysis suggested a role for inflammation and calcineurin signaling. Also several transcription factors were activated or deactivated. Linking these TFs to microarray data suggested an important role for glucocorticoid receptor (GR). The present study shows that an integrative approach, linking in vivo observations with changes in gene expression and TF activity leads to new insights in the molecular basis of post‐MI remodeling in a large animal. This study was supported by a grant from the Netherlands Heart Foundation (2005B234)