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Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure.

Tulacz D, Mackiewicz U, Maczewski M, Maciejak A, Gora M, Burzynska B - BMC Med Genomics (2013)

Bottom Line: Rats with small, moderate, and large MI size were included into the experiment two months after the operation.In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury.Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland. mgora@ibb.waw.pl.

ABSTRACT

Background: Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. The aim of this study was to investigate gene expression in the LV and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs).

Methods: MI was induced in rats by ligation of the proximal left coronary artery. Rats with small, moderate, and large MI size were included into the experiment two months after the operation. The development of heart failure was estimated by echocardiography and catheterization. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals.

Results: Only rats with a large MI developed extensive LV remodeling and heart failure. 840 transcripts were altered in LV of failing hearts, and especially numerous were those associated with the extracellular matrix. In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury. We showed that ceruloplasmin was similarly overexpressed in the heart and blood in response to HF, whereas downregulation of tetraspanin 12 was significant only in the PBMCs.

Conclusion: A large size of infarcted area is critical for progression of LV remodeling and HF development, associated with altered gene expression in the heart. Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.

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Related in: MedlinePlus

Enriched GO categories among differentially expressed genes in large-size infarction compared to sham-operated rats. Expression level were determined in left ventricle. Graphs show top results for the biological process (A), molecular function (B) and cellular component (C). In round brackets the p-value obtained from the AmiGO is shown, in square brackets the number of differentially expressed genes related to a particular GO term.
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Figure 2: Enriched GO categories among differentially expressed genes in large-size infarction compared to sham-operated rats. Expression level were determined in left ventricle. Graphs show top results for the biological process (A), molecular function (B) and cellular component (C). In round brackets the p-value obtained from the AmiGO is shown, in square brackets the number of differentially expressed genes related to a particular GO term.

Mentions: The genes identified as significantly altered in the L-MI group were further subjected to a gene ontology analysis (AmiGO) to find significant shared Gene Ontology terms. FigureĀ 2 presents only the GO terms with the most significant p-values, whereas in additional files we present complete results (Additional file 3). The analysis revealed that the molecular function of these genes is essentially connected to GO:0005488 binding and particularly to GO:0097367 carbohydrate derivative binding, GO:0005539 glycosaminoglycan binding, GO:1901681 sulfur compound binding, GO:0008201 heparin binding, GO:0005102 receptor binding and GO:0005515 protein binding. The biological processes are mainly associated with response to stimuli: GO:0010033 response to organic substance, GO:0009611 response to wounding and GO:0070887 cellular response to chemical stimulus. Cell adhesion GO:0007155 and small molecule metabolic process GO:0044281 were also at the top of significantly altered biological processes. Cellular component classification showed that most of the differently expressed genes were involved in GO:0005576 extracellular region (GO:0044421 extracellular region part, GO:0005615 extracellular space) and GO:0031012 extracellular matrix (GO:0005578 proteinaceous extracellular matrix, GO:0044420 extracellular matrix part).


Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure.

Tulacz D, Mackiewicz U, Maczewski M, Maciejak A, Gora M, Burzynska B - BMC Med Genomics (2013)

Enriched GO categories among differentially expressed genes in large-size infarction compared to sham-operated rats. Expression level were determined in left ventricle. Graphs show top results for the biological process (A), molecular function (B) and cellular component (C). In round brackets the p-value obtained from the AmiGO is shown, in square brackets the number of differentially expressed genes related to a particular GO term.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4226214&req=5

Figure 2: Enriched GO categories among differentially expressed genes in large-size infarction compared to sham-operated rats. Expression level were determined in left ventricle. Graphs show top results for the biological process (A), molecular function (B) and cellular component (C). In round brackets the p-value obtained from the AmiGO is shown, in square brackets the number of differentially expressed genes related to a particular GO term.
Mentions: The genes identified as significantly altered in the L-MI group were further subjected to a gene ontology analysis (AmiGO) to find significant shared Gene Ontology terms. FigureĀ 2 presents only the GO terms with the most significant p-values, whereas in additional files we present complete results (Additional file 3). The analysis revealed that the molecular function of these genes is essentially connected to GO:0005488 binding and particularly to GO:0097367 carbohydrate derivative binding, GO:0005539 glycosaminoglycan binding, GO:1901681 sulfur compound binding, GO:0008201 heparin binding, GO:0005102 receptor binding and GO:0005515 protein binding. The biological processes are mainly associated with response to stimuli: GO:0010033 response to organic substance, GO:0009611 response to wounding and GO:0070887 cellular response to chemical stimulus. Cell adhesion GO:0007155 and small molecule metabolic process GO:0044281 were also at the top of significantly altered biological processes. Cellular component classification showed that most of the differently expressed genes were involved in GO:0005576 extracellular region (GO:0044421 extracellular region part, GO:0005615 extracellular space) and GO:0031012 extracellular matrix (GO:0005578 proteinaceous extracellular matrix, GO:0044420 extracellular matrix part).

Bottom Line: Rats with small, moderate, and large MI size were included into the experiment two months after the operation.In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury.Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland. mgora@ibb.waw.pl.

ABSTRACT

Background: Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. The aim of this study was to investigate gene expression in the LV and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs).

Methods: MI was induced in rats by ligation of the proximal left coronary artery. Rats with small, moderate, and large MI size were included into the experiment two months after the operation. The development of heart failure was estimated by echocardiography and catheterization. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals.

Results: Only rats with a large MI developed extensive LV remodeling and heart failure. 840 transcripts were altered in LV of failing hearts, and especially numerous were those associated with the extracellular matrix. In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury. We showed that ceruloplasmin was similarly overexpressed in the heart and blood in response to HF, whereas downregulation of tetraspanin 12 was significant only in the PBMCs.

Conclusion: A large size of infarcted area is critical for progression of LV remodeling and HF development, associated with altered gene expression in the heart. Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.

Show MeSH
Related in: MedlinePlus