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This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: 107/4/1241    most recent 00564.2009v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Béguin, P. C. Articles by Calderone, A. PubMed PubMed Citation Articles by Béguin, P. C. Articles by Calderone, A.

The phenotype and potential origin of nestin⁺ cardiac myocyte-like cells following infarction

Department of ¹Physiology, Montreal Heart Institute and Université de Montréal; ; Department of ²Pharmacology, Montreal Heart Institute and Université de Montréal; and ; Department of ³Medicine, Montreal Heart Institute and Université de Montréal; ; Department of ⁴Research Center, Montreal Heart Institute and Université de Montréal; and ; ⁵Department of Paediatrics, Montreal Children's Hospital, Montreal, Quebec, Canada

Submitted 26 May 2009 ; accepted in final form 10 August 2009

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 β₁-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.

neural stem cells; ischemia; scar formation; β₁-adrenergic receptor; connexin-43