Human umbilical vein endothelial cells fuse with cardiomyocytes but do not activate cardiac gene expression.

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.