Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow-derived Progenitor Cells Mobilization and Homing to the Infarcted Heart.
Reparative response by bone marrow (BM)-derived progenitor cells (PCs) to ischemia is a multistep process that comprises the detachment from the BM endosteal niche through activation of osteoclasts and proteolytic enzymes (such as matrix metalloproteinases (MMPs)), mobilization to the circulation, and homing to the injured tissue. We previously showed that intramyocardial nerve growth factor gene transfer (NGF-GT) promotes cardiac repair following myocardial infarction (MI) in mice. Here, we investigate the impact of cardiac NGF-GT on postinfarction BM-derived PCs mobilization and homing at different time points after adenovirus-mediated NGF-GT in mice. Immunohistochemistry and flow cytometry newly illustrate the temporal profile of osteoclast and activation of MMP9, PCs expansion in the BM, and liberation/homing to the injured myocardium. NGF-GT amplified these responses and increased the BM levels of active osteoclasts and MMP9, which were not observed in MMP9-deficient mice. Taken together, our results suggest a novel role for NGF in BM-derived PCs mobilization/homing following MI.
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.|Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.|Current address: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Marco
M
Meloni
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Daniela
D
Cesselli
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.|BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Andrea
A
Caporali
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.
Giuseppe
G
Mangialardi
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.|Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Elisa
E
Avolio
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.
Carlotta
C
Reni
IRCCS Multimedica, Milan, Italy.
Orazio
O
Fortunato
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Stefania
S
Martini
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.
Paolo
P
Madeddu
Cardiology Department, University of Ferrara, Ferrara, Italy.
Marco
M
Valgimigli
Laboratory of Molecular Neurobiology, Nencki Institute, Warsaw, Poland.
Evgeni
E
Nikolaev
Laboratory of Molecular Neurobiology, Nencki Institute, Warsaw, Poland.
Leszek
L
Kaczmarek
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.
Gianni D
GD
Angelini
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Antonio P
AP
Beltrami
Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.|National Heart and Lung Institute, Imperial College London, London, UK.
Costanza
C
Emanueli
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology
D020932:Nerve Growth Factor; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse