title: G-CSF contributes at the healing of tunica media of arteriotomy-injured rat carotids by promoting differentiation of vascular smooth muscle cells.
abstract: Restenosis is a complex pathophysiological disease whose causative mechanisms are not fully understood. Previous studies allowed us to demonstrate the efficacy of bone marrow mesenchymal stromal cells (MSCs) transplantation in limiting the pathophysiological remodeling in a model of arteriotomy-induced (re) stenosis. In the current research we studied the effectiveness of G-CSF treatment on male rate rats that were subjected carotid arteriotomy in order to evaluate a potentially effective non-invasive strategy that recapitulates the MSC-mediated recovery of injured vessels. WKY male rats were subjected carotid arteriotomy and given a nine day treatment (3 days pre- to 6 days post-arteriotomy) with G-CSF or saline. Carotids were harvested 7 and 30 days following arteriotomy (early- and late-phase, respectively). Although morphometrical analysis did not reveal differences in lumen narrowing between G-CSF- and PBS-carotids 30 days following arteriotomy, we detected a noticeable conservative effect of G-CSF treatment on vascular wall morphology. Histological and molecular analysis revealed an increase in cellularity within the tunica media with a concomitant increase of the VSMCs differentiation markers both at early- and late-phases of (re) stenotic response in G-CSF-treated carotids (Sm22-alpha, Myocd, and Smtn). These findings were accompanied by the downregulation of oxidative stress-related genes in G-CSF-injured rats. The effect exerted by G-CSF in our model of arteriotomy-induced (re) stenosis seemed support the recovery of the architecture of the tunica media of injured vessels by: (i) inducing VSMCs differentiation; and (ii) limiting the oxidative-stress response induced by arteriotomy.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.|Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Second University of Naples, Naples, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rinaldi
authors.affiliation: Institute of Biomedicine and Bioresources (IBBR); CNR, Naples, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Finicelli
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Second University of Naples, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Donniacuo
authors.affiliation: Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Bernardo
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Second University of Naples, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gritti
authors.affiliation: Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Stefania Del
authors.initials: SD
authors.lastname: Gaudio
authors.affiliation: Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Forte
authors.affiliation: Institute of Biomedicine and Bioresources (IBBR); CNR, Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
authors.affiliation: Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Cipollaro
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Second University of Naples, Naples, Italy.|Institute of Biomedicine and Bioresources (IBBR); CNR, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Biotechnology, and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor