title: The cardiac neural stem cell phenotype is compromised in streptozotocin-induced diabetic cardiomyopathy.
abstract: Neural stem cells were identified in the rat heart and during scar formation and healing participated in sympathetic fiber sprouting and angiogenesis. In the setting of diabetes, impaired wound healing represents a typical pathological feature. These findings provided the impetus to test the hypothesis that experimental diabetes adversely influenced the phenotype of cardiac neural stem cells. Streptozotocin (STZ)-induced diabetic rats were associated with elevated plasma glucose levels, significant loss of body weight and left ventricular contractile dysfunction. In the heart of STZ-diabetic rats, the density of nestin immunoreactive processes emanating from cardiac neural stem cells were reduced. The latter finding was reaffirmed as nestin protein expression was significantly decreased in the heart of STZ-diabetic rats and associated with a concomitant reduction of nestin mRNA. Employing the TUNEL assay, the loss of nestin expression in STZ-diabetic rats was not attributed to widespread cardiac neural stem cell apoptosis. Insulin administration to STZ-diabetic rats with established hyperglycaemia led to a modest recovery of nestin protein expression in cardiac neural stem cells. By contrast, the administration of insulin immediately after STZ injection improved plasma glucose levels and significantly attenuated the loss of nestin protein expression. These data highlight the novel observation that nestin protein expression in cardiac neural stem cells was significantly reduced in STZ-induced type I diabetic rats. The aberrant cardiac neural stem cell phenotype may compromise their biological role and predispose the diabetic heart to maladaptive healing following ischemic injury.
authors.affiliation: Département de Physiologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Viviane
authors.initials: V
authors.lastname: El-Helou
authors.forename: Cindy
authors.initials: C
authors.lastname: Proulx
authors.forename: Pauline
authors.initials: P
authors.lastname: Béguin
authors.forename: John
authors.initials: J
authors.lastname: Assimakopoulos
authors.forename: Hugues
authors.initials: H
authors.lastname: Gosselin
authors.forename: Robert
authors.initials: R
authors.lastname: Clement
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Julie-Emilie
authors.initials: JE
authors.lastname: Huot-Marchand
authors.forename: Denis
authors.initials: D
authors.lastname: Deblois
authors.forename: Claude
authors.initials: C
authors.lastname: Lajoie
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D009202:Cardiomyopathies / Q000209:etiology / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009929:Organ Size; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D003907:Dexamethasone