Cardiovascular Research Advance Access originally published online on November 30, 2007
Cardiovascular Research 2008 77(4):722-731; doi:10.1093/cvr/cvm080
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Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival
1 Klinikum der Ludwig-Maximilians-Universität München - Grosshadern, Med. Klinik und Poliklinik I, Marchioninistr. 15, D-81377 Munich, Germany
2 Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany
3 Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany
4 Institute of Veterinary Pathology, Ludwig-Maximilians-University, Munich, Germany
5 Department of Experimental Cardiology, UMC, Utrecht, The Netherlands
* Corresponding author. Tel: +49 89 7095 6095; fax: +49 89 7095 6094. E-mail address: wolfgang.franz{at}med.uni-muenchen.de
Aims: An ongoing concept is that stem cells have the potential to regenerate the injured myocardium. In addition to direct vasorelaxing effects on the vasculature, which are mediated by an increased cAMP production leading to a decreased calcium influx in smooth muscle cells, parathyroid hormone (PTH) was recently shown to facilitate stem cell mobilization. Therefore, we analysed in a murine model of experimental myocardial infarction (MI) the influence of PTH treatment on survival, functional parameters, stem cell migration, and expression of vascular endothelial growth factor A (VEGF-A).
Methods and results: Mice (C57BL/6) were treated with PTH (80 µg/kg/d) for up to 14 days after coronary artery ligation. Functional and immunohistochemical analyses were performed at days 6 and 30 after MI. Stem cells and VEGF expression in the myocardium were analysed by FACS and qRT-PCR at day 2 after MI. PTH-treated animals revealed a significant improvement of post-MI survival and myocardial function that was related to a subsequent reduction of left ventricular wall thinning and scar extension. Infarcted hearts of PTH-treated mice revealed increased numbers of CD45+/CD34+ progenitor cells as well as an upregulation of VEGF-A mRNA associated with increased neovascularization and cell survival.
Conclusions: PTH application after MI increases migration of angiogenic CD45+/CD34+ progenitor cells to the ischaemic heart, which may attenuate ischaemic cardiomyopathy. As PTH is already used in patients with osteoporosis, our findings may have a direct impact on the initiation of clinical studies in patients with ischaemic heart disease.
KEYWORDS Parathyroid hormone; Myocardial infarction; Neovascularization; VEGF; Stem cells
Time for primary review: 37 days
The first two authors equally contributed to this work.
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