Bone marrow-derived progenitor cells contribute to lung remodelling after myocardial infarction.
BACKGROUND
Congestive heart failure (CHF) causes structural modifications of the lungs that contribute to the functional limitations of affected subjects. We hypothesized that bone marrow-derived progenitor cells could contribute to lung structural remodelling after myocardial infarction (MI).


METHODS
Wistar rats were irradiated and received a bone marrow transplant (BMT) from green fluorescent protein (GFP) transgenic rats, followed 5 weeks later by coronary artery ligation or sham operation. Five weeks after MI, lung immunofluorescence studies were performed and GFP expression evaluated by Western immunoblotting.


RESULTS
After MI, rats developed lung structural remodelling characterized by myofibroblast (MF) proliferation in the alveolar septa. After BMT, some GFP+ cells were found in the lungs of sham animals. The amount of GFP+ cells in the lungs of MI rats was greatly increased with evidence of differentiation into MFs, as evaluated by co-localization correlation analysis with smooth muscle alpha-actin (P<.01). These cells were particularly abundant in the perivenular regions where they incorporated into the wall of blood vessels. There was a threefold increase in lung GFP protein expression after MI (P=.01).


CONCLUSIONS
After MI, bone marrow-derived progenitor differentiates into lung MFs. This novel pathophysiologic process may contribute to the pulmonary manifestations of CHF and could have significant therapeutic implications.
Dupuis
Jocelyn
J
Research Center, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada H1T 1C8. jocelyn.dupuis@bellnet.ca <jocelyn.dupuis@bellnet.ca>
Préfontaine
Annick
A
Villeneuve
Louis
L
Ruel
Nathalie
N
Lefebvre
Frédéric
F
Calderone
Angelino
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014916:Whole-Body Irradiation
D000199:Actins; D049452:Green Fluorescent Proteins; C498862:Acta2 protein, rat