The phenotype and potential origin of nestin+ cardiac myocyte-like cells following infarction.
Nestin+ cardiac myocyte-like cells were detected in the peri-infarct/infarct region of the ischemically damaged heart. The present study was undertaken to elucidate the phenotype and potential origin of nestin+ cardiac myocyte-like cells and identify stimuli implicated in their appearance. In the infarcted human and rat heart, nestin+ cardiac myocyte-like cells were morphologically and structurally immature, exhibited a desmin-immunoreactive striated phenotype, expressed the beta(1)-adrenergic receptor, and associated with an aberrant pattern of connexin-43 expression and/or organization. Nestin+ cardiac myocyte-like cells were detected 24 h postischemic injury and persisted in the infarcted rat heart for 9 mo. In the normal rat heart, cardiac progenitor transcriptional factors Nkx2.5/GATA4 were detected in a subpopulation of nestin+ neural stem cells. Following an ischemic insult, nestin+/Nkx2.5+ neural stem cells migrated to the peri-infarct/infarct region and appeared to be in a primordial state of differentiation to a nestin+ cardiac myocyte-like cell. The exposure of adult male rats to normobaric hypoxia (12% O2) for 10 days failed to promote the appearance of nestin+ cardiac myocyte-like cells. Following osmotic pump delivery of isoproterenol to normal adult rats, nestin+ cardiac myocyte-like cells were detected, albeit the response was modest and secondary to tissue loss. Thus ischemia-induced appearance of nestin+ cardiac myocyte-like cells apparently represents an adaptive response to heal the infarcted heart. Nkx2.5/GATA4 expression in a subpopulation of resident neural stem cells provides the appropriate phenotype for their potential differentiation to a nestin+ cardiac myocyte-like cell.
Béguin
Pauline C
PC
angelo.calderone@umontreal.ca
El-Helou
Viviane
V
Assimakopoulos
John
J
Clément
Robert
R
Gosselin
Hugues
H
Brugada
Ramon
R
Villeneuve
Louis
L
Rohlicek
Charles V
CV
Del Duca
Danny
D
Lapointe
Nathalie
N
Rouleau
Jean L
JL
Calderone
Angelino
A
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D050991:GATA4 Transcription Factor / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D055104:Infusions, Subcutaneous; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013564:Sympathetic Nervous System / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D018031:Connexin 43; D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C524161:Nkx2-5 protein, rat; D018342:Receptors, Adrenergic, beta-1; D014157:Transcription Factors; D007545:Isoproterenol