Stem cell-related cardiac gene expression early after murine myocardial infarction.
OBJECTIVE
Clinical experimental stem cell therapy after myocardial infarction appears feasible, but its use has preceded the understanding of the working mechanism. The ischemic recipient cardiac environment is determinative for the attraction and subsequent fate of stem cells. Here, we studied expression levels of genes that are anticipated to be essential for adequate stem cell-based cardiac repair at various time-points during the 1 month period following myocardial infarction (MI).


METHODS
Gene expression in the hearts of mice that underwent MI by permanent or transient (30 min) ligation of the coronary artery was monitored using quantitative RT-PCR analysis of mRNA isolated from whole heart sections as well as from specific, laser micro-dissected, regions of sections. Protein expression was performed by immunohistochemical stainings and Western blot analysis.


RESULTS
Many inflammatory genes were highly expressed for at least 1 week after MI. The expression of pro-angiogenic genes such as bFGF, VEGF-A and VEGF-R2 changed only marginally post-MI. Markers used to test stem cell gene expression remained unchanged post-MI with the exception of G-CSF and GM-CSF, which are genes that are also known to enhance the inflammatory response. Analysis of micro-dissected regions revealed that SDF-1, SCF (both stem cell attractants) and VEGF-R2 (involved in angiogenesis) gene expression was slightly decreased especially in the infarcted region.


CONCLUSIONS
Genes that are generally considered to participate in stem cell-related processes and angiogenesis were not upregulated after MI, whereas the inflammatory gene expression dominated. Modulation of this imbalance might be of value for stem cell-mediated therapy.
Vandervelde
Susanne
S
University of Groningen, University Medical Center Groningen, Department of Pathology and Laboratory Medicine, Section Medical Biology (MB Z1.17), Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
van Luyn
Marja J A
MJ
Rozenbaum
Mark H
MH
Petersen
Arjen H
AH
Tio
Rene A
RA
Harmsen
Martin C
MC
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D018932:Chemokine CCL2 / Q000235:genetics; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000235:genetics; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008026:Ligation; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D042282:Microdissection / Q000379:methods; D018613:Microscopy, Confocal; D023421:Models, Animal; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017467:Receptors, Erythropoietin / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000235:genetics
C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D040301:Vascular Endothelial Growth Factor Receptor-2