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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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Heat map representing hierarchical clustering of 73 differentially expressed genes related to extracellular matrix (GO:0031012). Each column corresponds to a single microarray whereas each row represents expression profile of a single gene. Red stand for the positive values in the gene expression and green for the negative ones. Sham - sham-operated; S-MI - small-size infarction; M-MI - moderate-size infarction; L-MI - large-size infarction.
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Figure 3: Heat map representing hierarchical clustering of 73 differentially expressed genes related to extracellular matrix (GO:0031012). Each column corresponds to a single microarray whereas each row represents expression profile of a single gene. Red stand for the positive values in the gene expression and green for the negative ones. Sham - sham-operated; S-MI - small-size infarction; M-MI - moderate-size infarction; L-MI - large-size infarction.

Mentions: Extracellular matrix remodelling is the critical event in pathology of HF. For that reason, a focused hierarchical clustering analysis was done for transcripts annotated as GO:0031012 extracellular matrix (Additional file 4) to show their expression profiles in LV samples from individual rats (FigureĀ 3). This analysis revealed a clearly distinct gene expression profile of the selected genes in rats with L-MI that clustered separately from the other groups. Interestingly, all these genes were upregulated in the L-MI group, with one exception - vitronectin (Vnt), although they are involved in both ECM deposition and degradation.


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)

Heat map representing hierarchical clustering of 73 differentially expressed genes related to extracellular matrix (GO:0031012). Each column corresponds to a single microarray whereas each row represents expression profile of a single gene. Red stand for the positive values in the gene expression and green for the negative ones. Sham - sham-operated; S-MI - small-size infarction; M-MI - moderate-size infarction; L-MI - large-size infarction.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Heat map representing hierarchical clustering of 73 differentially expressed genes related to extracellular matrix (GO:0031012). Each column corresponds to a single microarray whereas each row represents expression profile of a single gene. Red stand for the positive values in the gene expression and green for the negative ones. Sham - sham-operated; S-MI - small-size infarction; M-MI - moderate-size infarction; L-MI - large-size infarction.
Mentions: Extracellular matrix remodelling is the critical event in pathology of HF. For that reason, a focused hierarchical clustering analysis was done for transcripts annotated as GO:0031012 extracellular matrix (Additional file 4) to show their expression profiles in LV samples from individual rats (FigureĀ 3). This analysis revealed a clearly distinct gene expression profile of the selected genes in rats with L-MI that clustered separately from the other groups. Interestingly, all these genes were upregulated in the L-MI group, with one exception - vitronectin (Vnt), although they are involved in both ECM deposition and degradation.

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