Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival.
OBJECTIVE
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).


RESULTS
Mice (C57BL/6) were treated with PTH (80 microg/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.
Klinikum der Ludwig-Maximilians-Universität München Grosshadern, Med Klinik und Poliklinik I, Marchioninistr 15, Munich, Germany.
Marc-Michael
MM
Zaruba
Bruno C
BC
Huber
Stefan
S
Brunner
Elisabeth
E
Deindl
Robert
R
David
Rebekka
R
Fischer
Gerald
G
Assmann
Nadja
N
Herbach
Sebastian
S
Grundmann
Ruediger
R
Wanke
Josef
J
Mueller-Hoecker
Wolfgang-Michael
WM
Franz
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019899:Paracrine Communication; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D018952:Antigens, CD34; D002317:Cardiovascular Agents; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse