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

Abstract

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.

• Authors: Pauline C Béguin, Viviane El-Helou, John Assimakopoulos, Robert Clément, Hugues Gosselin, Ramon Brugada, Louis Villeneuve, Charles V Rohlicek, Danny Del Duca, Nathalie Lapointe, Jean L Rouleau, Angelino Calderone
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 107 Issue 4 Pg. 1241-8 (Oct 2009) ISSN: 1522-1601 [Electronic] United States
• PMID: 19679743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Agonists
• Connexin 43
• GATA4 Transcription Factor
• Gata4 protein, rat
• Homeobox Protein Nkx-2.5
• Homeodomain Proteins
• Intermediate Filament Proteins
• NES protein, human
• Nerve Tissue Proteins
• Nes protein, rat
• Nestin
• Nkx2-5 protein, rat
• Receptors, Adrenergic, beta-1
• Transcription Factors
• Isoproterenol

Topics

• Adrenergic beta-Agonists (administration & dosage)
• Animals
• Cell Differentiation
• Cell Movement
• Connexin 43 (metabolism)
• Disease Models, Animal
• GATA4 Transcription Factor (metabolism)
• Homeobox Protein Nkx-2.5
• Homeodomain Proteins (metabolism)
• Humans
• Hypoxia (metabolism, pathology)
• Infusions, Subcutaneous
• Intermediate Filament Proteins (metabolism)
• Isoproterenol (administration & dosage)
• Male
• Myocardial Infarction (metabolism, pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Nerve Tissue Proteins (metabolism)
• Nestin
• Neurons (drug effects, metabolism, pathology)
• Phenotype
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, beta-1 (metabolism)
• Stem Cells (drug effects, metabolism, pathology)
• Sympathetic Nervous System (metabolism)
• Time Factors
• Transcription Factors (metabolism)