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Cardiovascular Research 2007 73(4):783-793; doi:10.1016/j.cardiores.2006.11.030
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Copyright © 2006, European Society of Cardiology

Stem cell-related cardiac gene expression early after murine myocardial infarction

Susanne Vanderveldea, Marja J.A. van Luyna, Mark H. Rozenbauma, Arjen H. Petersena, Rene A. Tiob and Martin C. Harmsena,*

aUniversity 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
bDepartment of Cardiology, Thoraxcenter, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

* Corresponding author. Tel.: +31 50 361 47 76; fax: +31 50 361 99 11. Email address: m.c.harmsen{at}med.umcg.nl

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.

Conclusion: 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.

KEYWORDS Myocardial infarction; Gene expression; Stem cells; Angiogenesis; Cytokines; Growth factors

Time for primary review 34 days


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