Human microvascular endothelial cells immortalized with human telomerase catalytic protein: a model for the study of in vitro angiogenesis

Biochem Biophys Res Commun. 2004 Sep 3;321(4):788-94. doi: 10.1016/j.bbrc.2004.07.033.

Abstract

Human microvascular endothelial cell-1 (HMEC-1) generated by transfection with SV40 large T antigen has been the prevailing model for in vitro studies on endothelium. However, the transduction of SV40 may lead to unwanted cell behaviors which are absent in primary cells. Thus, establishing a new microvascular endothelial cell line, which is capable of maintaining inherent features of primary endothelial cells, appears to be extremely important. Here, we immortalized primary human microvascular endothelial cells (pHMECs) by engineering the human telomerase catalytic protein (hTERT) into the cells. Endothelial cell-specific markers were examined and the angiogenic responses were characterized in these cells (termed as HMVECs, for human microvascular endothelial cells). We found that VEGF receptor 2 (Flk-1/KDR), tie1, and tie2 expression is preserved in HMVEC, whereas Flk-1/KDR is absent in HMEC-1. In addition, HMVEC showed similar angiogenic responses to VEGF as HMEC-1. Furthermore, the HMVEC line was found to generate a prominent angiogenic response to periostin, a potent angiogenic factor identified recently. The data indicate that HMVEC may serve as a suitable in vitro endothelium model.

MeSH terms

  • Cell Line
  • DNA-Binding Proteins
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Genetic Engineering
  • Humans
  • Models, Cardiovascular*
  • Neovascularization, Physiologic* / drug effects
  • Receptor, TIE-1 / metabolism
  • Receptor, TIE-2 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Telomerase / genetics
  • Telomerase / physiology*
  • Transformation, Genetic
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • DNA-Binding Proteins
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-2
  • Telomerase