title: Human umbilical vein endothelial cells fuse with cardiomyocytes but do not activate cardiac gene expression.
abstract: It was recently reported that human umbilical endothelial vein cells (HUVECs) transdifferentiate and express cardiac genes when co-cultured with rat neonatal cardiomyocytes (Condorelli et al. (2001)). If substantiated and optimized, this phenomenon could have many therapeutic applications. We re-investigated the HUVEC-rat neonatal cardiomyocyte co-culture system but detected cardiomyocyte markers (sarcomeric myosin) in only 1.2% of the cells containing nuclei that were immuno-positive for human nuclear antigen (HNA); and the frequency of such cells was not enhanced in co-cultures containing more embryonic cardiomyocytes. Because the majority of HNA-positive/myosin-positive cells were binucleated, we tested the hypothesis that these cells resulted from HUVEC-cardiomyocyte fusion rather than from HUVEC transdifferentiation. Analysis with a Cre/lox recombination assay indicated that virtually all HUVECs containing cardiac markers had fused with cardiomyocytes. To determine whether human cardiomyocyte genes are activated at low levels in HUVEC-cardiomyocyte co-cultures, quantitative RT-PCR was performed with primers specific for human beta-MyHC and cTnI. We found no evidence for transcriptional activation of these genes. None of our data support conversion of HUVECs to cardiomyocytes.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Welikson
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kaestner
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hauschka
mesh_terms: D000818:Animals; D002459:Cell Fusion / Q000379:methods; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D009928:Organ Specificity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology*