Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-8-23
pubmed:abstractText
The connexin43 knockout (Cx43alpha1 KO) mouse dies at birth from outflow obstruction associated with infundibular pouches. To elucidate the origin of the infundibular pouches, we used microarray analysis to investigate gene expression changes in the pouch tissue. We found elevated expression of many genes encoding markers for vascular smooth muscle (VSM), endothelial cells, and fibroblasts, cell types that are epicardially derived and essential for coronary vasculogenesis. This was accompanied by increased expression of VEGF and genes in the TGFbeta and VEGF/Notch/Eph cell-signaling pathways known to regulate vasculogenesis/angiogenesis. Using immunohistochemistry and a VSM lacZ reporter gene, we confirmed an abundance of ectopic VSM and endothelial cells in the infundibular pouch and in some regions of the right ventricle forming secondary pouches. This was associated with distinct thinning of the compact myocardium. TUNEL labeling showed increased apoptosis in the pouch tissue, in agreement with the finding of altered expression of many apoptotic genes. Defects in vascular remodeling were indicated by a marked reduction in the branching complexity of the distal coronary arteries. In the near term KO mouse, we also observed a profusion of large coronary vascular plexuses subepicardially. This was associated with elevated epicardial expression of VEGF and abnormal epicardial cell morphology. Together, these observations indicate that dysregulated coronary vasculogenesis plays a pivotal role in formation of the infundibular pouches and suggests an essential role for Cx43alpha1 gap junctions in coronary vasculogenesis and vascular remodeling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0012-1606
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
479-98
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16039638-Animals, pubmed-meshheading:16039638-Apoptosis, pubmed-meshheading:16039638-Biological Markers, pubmed-meshheading:16039638-Connexin 43, pubmed-meshheading:16039638-Coronary Vessels, pubmed-meshheading:16039638-Crosses, Genetic, pubmed-meshheading:16039638-Endothelial Cells, pubmed-meshheading:16039638-Endothelium, Vascular, pubmed-meshheading:16039638-Fibroblasts, pubmed-meshheading:16039638-Gene Expression Regulation, Developmental, pubmed-meshheading:16039638-Genes, Reporter, pubmed-meshheading:16039638-Heart, pubmed-meshheading:16039638-Heterozygote, pubmed-meshheading:16039638-Immunohistochemistry, pubmed-meshheading:16039638-Membrane Proteins, pubmed-meshheading:16039638-Mice, pubmed-meshheading:16039638-Mice, Inbred C57BL, pubmed-meshheading:16039638-Mice, Knockout, pubmed-meshheading:16039638-Microarray Analysis, pubmed-meshheading:16039638-Models, Biological, pubmed-meshheading:16039638-Muscle, Smooth, Vascular, pubmed-meshheading:16039638-Neovascularization, Physiologic, pubmed-meshheading:16039638-Receptors, Notch, pubmed-meshheading:16039638-Signal Transduction, pubmed-meshheading:16039638-Transforming Growth Factor beta, pubmed-meshheading:16039638-Vascular Endothelial Growth Factor A
pubmed:year
2005
pubmed:articleTitle
Connexin43 deficiency causes dysregulation of coronary vasculogenesis.
pubmed:affiliation
Laboratory of Developmental Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Building 50/Room 4537, Bethesda, MD 20892-8019, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural