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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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Principal component analysis of PBMCs gene expression profiles. PCA plot shows the first three principal components of microarray data in respect to their correlation. Sham - sham-operated; L-MI - large-size infarction.
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Figure 4: Principal component analysis of PBMCs gene expression profiles. PCA plot shows the first three principal components of microarray data in respect to their correlation. Sham - sham-operated; L-MI - large-size infarction.

Mentions: PBMCs are considered to be an ideal surrogate tissue to reflect changes occurring in major human organs [14]. Therefore, a further microarray analysis was performed to evaluate if and how the progressive heart failure in rats with L-MI affected the gene expression patterns in PBMCs. Global transcriptomic profiles analysed by PCA demonstrated a separation between the sham-operated rats and rats with L-MI that was less clear-cut than that found for the heart tissue (Figure 4). A list of differentially expressed genes was determined with the cutoff criteria described in Materials and Methods. The expression of 72 (38 - upregulated, 34 - downregulated) well-annotated transcripts was altered in PBMCs in the L-MI rats 2 months after the operation in comparison with sham-operated rats (Additional file 5). The AmiGO analysis showed no significantly enriched GO terms, while the DAVID Functional Annotation Tool identified several categories. The molecular function of those genes is mainly connected to GO:0005488 binding, especially GO:0005529 sugar and GO:0005537 mannose binding. Biological processes are associated with response to stimuli: GO:0014070 response to organic cyclic substance and GO:0009607 response to biotic stimulus (GO:0009617 response to bacterium stimuli, GO:0051007 response to other organism). Cellular component classification showed that most of those genes were connected with GO:0016020 membrane. Complete results are shown in Additional file 6.


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)

Principal component analysis of PBMCs gene expression profiles. PCA plot shows the first three principal components of microarray data in respect to their correlation. Sham - sham-operated; L-MI - large-size infarction.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Principal component analysis of PBMCs gene expression profiles. PCA plot shows the first three principal components of microarray data in respect to their correlation. Sham - sham-operated; L-MI - large-size infarction.
Mentions: PBMCs are considered to be an ideal surrogate tissue to reflect changes occurring in major human organs [14]. Therefore, a further microarray analysis was performed to evaluate if and how the progressive heart failure in rats with L-MI affected the gene expression patterns in PBMCs. Global transcriptomic profiles analysed by PCA demonstrated a separation between the sham-operated rats and rats with L-MI that was less clear-cut than that found for the heart tissue (Figure 4). A list of differentially expressed genes was determined with the cutoff criteria described in Materials and Methods. The expression of 72 (38 - upregulated, 34 - downregulated) well-annotated transcripts was altered in PBMCs in the L-MI rats 2 months after the operation in comparison with sham-operated rats (Additional file 5). The AmiGO analysis showed no significantly enriched GO terms, while the DAVID Functional Annotation Tool identified several categories. The molecular function of those genes is mainly connected to GO:0005488 binding, especially GO:0005529 sugar and GO:0005537 mannose binding. Biological processes are associated with response to stimuli: GO:0014070 response to organic cyclic substance and GO:0009607 response to biotic stimulus (GO:0009617 response to bacterium stimuli, GO:0051007 response to other organism). Cellular component classification showed that most of those genes were connected with GO:0016020 membrane. Complete results are shown in Additional file 6.

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