title: Altered expression of connexin 43 and related molecular partners in a pig model of left ventricular dysfunction with and without dipyrydamole therapy.
abstract: Gap junctions (GJ) mediate electrical coupling between cardiac myocytes, allowing the spreading of the electrical wave responsible for synchronized contraction. GJ function can be regulated by modulation of connexon densities on membranes, connexin (Cx) phosphorylation, trafficking and degradation. Recent studies have shown that adenosine (A) involves Cx43 turnover in A1 receptor-dependent manner, and dipyridamole increases GJ coupling and amount of Cx43 in endothelial cells. As the abnormalities in GJ organization and regulation have been described in diseased myocardium, the aim of the present study was to assess the regional expression of molecules involved in GJ regulation in a model of left ventricular dysfunction (LVD). For this purpose the distribution and quantitative expression of Cx43, its phosphorylated form pS368-Cx43, PKC phosphorylated substrates, RhoA and A receptors, were investigated in experimental models of right ventricular-pacing induced LVD, undergoing concomitant dipyridamole therapy or placebo, and compared with those obtained in the myocardium from sham-operated minipigs. Results demonstrate that an altered pattern of factors involved in Cx43-made GJ regulation is present in myocardium of a dysfunctioning left ventricle. Furthermore, dipyridamole treatment, which shows a mild protective role on left ventricular function, seems to act through modulating the expression and activation of these factors as confirmed by in vitro experiments on cardiomyoblastic cell line H9c2 cells.
authors.affiliation: CNR Institute of Clinical Physiology, Laboratory Biochemistry and Molecular Biology, CNR, Italy Clinical Physiology, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Ry
authors.affiliation: Department of Clinic and Experimental Medicine, Section Histology, University of Pisa, Pisa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Moscato
authors.affiliation: Department of Clinic and Experimental Medicine, Section Histology, University of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: CNR Institute of Clinical Physiology, Laboratory Biochemistry and Molecular Biology, CNR, Italy Clinical Physiology, Pisa, Italy.
authors.forename: Maria Aurora
authors.initials: MA
authors.lastname: Morales
authors.affiliation: Department of Clinic and Experimental Medicine, Section Histology, University of Pisa, Pisa, Italy.
authors.forename: Amelio
authors.initials: A
authors.lastname: Dolfi
authors.affiliation: G Monasterio Foundation, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Burchielli
authors.affiliation: CNR Institute of Clinical Physiology, Laboratory Biochemistry and Molecular Biology, CNR, Italy Clinical Physiology, Pisa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cabiati
authors.affiliation: Department of Clinic and Experimental Medicine, Section Histology, University of Pisa, Pisa, Italy. Electronic address: letizia.mattii@med.unipi.it.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mattii
mesh_terms: D000818:Animals; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004176:Dipyridamole / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004562:Electrocardiography; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018031:Connexin 43; D004176:Dipyridamole
keywords: Adenosine receptor; Connexin 43; Dipyridamole; Pig model; Protein kinase C; RhoA; Ventricular dysfunction