Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach. 2011

Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
Division of Experimental Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, P. O. Box 2040, 3000 CA Rotterdam, The Netherlands.

Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR < 0.05). Of these differentially expressed genes, the promoter regions of the human homologs were searched for common TF binding sites (TFBS). Eighteen TFBS were overrepresented >two-fold (p < 0.01) in upregulated and 13 in downregulated genes. Left ventricular nuclear protein extracts were assayed for DNA-binding activity by protein/DNA array. Out of 345 DNA probes, 30 showed signal intensity changes >two-fold. Five TFs were identified in both TFBS and protein/DNA array analyses, which showed matching changes for COUP-TFII and glucocorticoid receptor (GR) only. Treatment of swine with the GR antagonist mifepristone after MI reduced the post-MI increase in LV mass, but LV dilation remained unaffected. Thus, using an unbiased approach to study post-MI LV remodeling in a physiologically relevant large animal model, we identified COUP-TFII and GR as potential key mediators of post-MI remodeling.

UI MeSH Term Description Entries
D008297 Male Males
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D011965 Receptors, Glucocorticoid Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example. Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004452 Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Echocardiography, Contrast,Echocardiography, Cross-Sectional,Echocardiography, M-Mode,Echocardiography, Transthoracic,Echocardiography, Two-Dimensional,Transthoracic Echocardiography,2-D Echocardiography,2D Echocardiography,Contrast Echocardiography,Cross-Sectional Echocardiography,Echocardiography, 2-D,Echocardiography, 2D,M-Mode Echocardiography,Two-Dimensional Echocardiography,2 D Echocardiography,Cross Sectional Echocardiography,Echocardiography, 2 D,Echocardiography, Cross Sectional,Echocardiography, M Mode,Echocardiography, Two Dimensional,M Mode Echocardiography,Two Dimensional Echocardiography
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D051837 COUP Transcription Factor II A COUP transcription factor that negatively regulates GENETIC TRANSCRIPTION and competes with other hormone receptors for the common response element AGGTCA. It can also stimulate transcription of genes involved in the metabolism of GLUCOSE and CHOLESTEROL. ApoAI Regulatory Protein-1,Apolipoprotein AI Regulatory Protein 1,COUP Transcription Factor 2,COUP-TF2 Protein,COUP-TFII Protein,Chicken Ovalbumin Upstream Promoter-Transcription Factor II,Nuclear Receptor NR2F2,Nuclear Receptor Subfamily 2, Group F, Member 2,ApoAI Regulatory Protein 1,COUP TF2 Protein,COUP TFII Protein,Chicken Ovalbumin Upstream Promoter Transcription Factor II

Related Publications

Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
November 1995, Cardiologia (Rome, Italy),
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
May 1992, Archives des maladies du coeur et des vaisseaux,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
January 1995, Annual review of medicine,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
May 2003, Nihon rinsho. Japanese journal of clinical medicine,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
January 2014, American journal of physiology. Heart and circulatory physiology,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
March 2016, Artificial organs,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
May 2003, Circulation,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
October 2007, Journal of the American College of Cardiology,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
December 1991, Archives des maladies du coeur et des vaisseaux,
Diederik W D Kuster, and Daphne Merkus, and Andreas Kremer, and Wilfred F J van Ijcken, and Vincent J de Beer, and Adrie J M Verhoeven, and Dirk J Duncker
January 2011, Indian heart journal,
Copied contents to your clipboard!