Document Detail


Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts.
MedLine Citation:
PMID:  11164852     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Within the adult heart, it is convention to distinguish the conduction system and working (atrial and ventricular) myocardium. The adult conduction system (CS) comprises the sinoatrial (SAN), and atrioventricular (AVN) nodes, the atrioventricular bundle (AVB), the bundle branches and the peripheral Purkinje fibers, each of which display distinct functional properties and distinct profile of gene expression. Characterization of the mouse cardiac conduction system during development is rudimentary at present, even though genetically-modified mice are an increasing source of information regarding cardiac function and embryonic heart development. METHODS: We have performed a detailed study of the pattern of expression of myosin heavy chain (MHC), myosin light chain (MLC), troponin I (TnI) isoforms, connexin 43 (Cx43), desmin and alpha-smooth muscle actin (alpha-SMA), in the ventricular conduction system of normal and congenitally malformed mouse hearts (iv background) from embryonic day 14.5 to 19.5. RESULTS: The AVN is characterized by co-expression of MHC and MLC isoforms and no detectable expression of Cx43, desmin or alpha-SMA. The AVB expresses betaMHC and MLC2v, but no alphaMHC, MLC2a, Cx43, desmin or alpha-SMA. The right and left bundle branches display enhanced expression of desmin and alpha-SMA but no Cx43. The normal expression profile is maintained in congenitally malformed hearts such as double-outlet right ventricle and common atrioventricular canal. Three-dimensional reconstruction of the conduction system shows normal arrangement of the bundle branches in congenitally malformed hearts, but abnormal location and/or extension of the AVN. CONCLUSIONS: Molecular characterization allows to follow the development of the CS in both, normal and malformed mouse hearts. Normal phenotypic expression of the CS is independent of heart situs but shows minor modifications in the presence of heart malformations. It is concluded that the AVN derives from the atrioventricular canal myocardium, the bundle of His from the ventricular myocardium, and the bundle branches from the ventricular trabeculations. Our results do not provide evidence to support an extra-cardiac origin of the ventricular CS.
Authors:
D Franco; J M Icardo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  49     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-04-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  417-29     Citation Subset:  IM    
Affiliation:
Department of Experimental Biology, Faculty of Experimental and Health Sciences, University of Jaén, Paraje Las Lagunillas s/n, 23071, Jaén, Spain. dfranco@ujaen.es
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics,  metabolism
Animals
Atrioventricular Node / embryology,  metabolism
Bundle of His / embryology,  metabolism
Connexin 43 / genetics,  metabolism
Desmin / genetics,  metabolism
Gestational Age
Heart Atria / embryology,  metabolism
Heart Conduction System / embryology*,  metabolism
Heart Defects, Congenital / embryology*,  metabolism
Heart Ventricles / embryology,  metabolism
Image Processing, Computer-Assisted
Immunohistochemistry
In Situ Hybridization
Mice
Mice, Mutant Strains
Myosin Heavy Chains / genetics,  metabolism
Myosin Light Chains / genetics,  metabolism
Protein Isoforms / genetics,  metabolism
RNA, Messenger / analysis
Sinoatrial Node / embryology,  metabolism
Troponin I / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Actins; 0/Connexin 43; 0/Desmin; 0/Myosin Heavy Chains; 0/Myosin Light Chains; 0/Protein Isoforms; 0/RNA, Messenger; 0/Troponin I
Comments/Corrections
Comment In:
Cardiovasc Res. 2001 Jun;50(3):610-2   [PMID:  11392355 ]

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