REGULATION OF ANGIOPOIETIN-2 MESSENGER-RNA LEVELS IN BOVINE MICROVASCULAR ENDOTHELIAL-CELLS BY CYTOKINES AND HYPOXIA

Angiopoietin-2 (Ang2) is a ligand for the endothelial cell tyrosine ki nase receptor Tie2 and counteracts blood vessel maturation/stability m ediated by angiopoietin-1 (Ang1), the other known ligand of Tie2. Usin g degenerate oligonucleotides and reverse transcriptase-polymerase cha in reaction, we have screened bovine microvascular endothelial (BME), aortic, lymphatic, pulmonary artery, and transformed fetal aortic endo thelial cells, as well as rat smooth muscle cells for Ang1 and Ang2 ex pression. Except for high Ang2 mRNA levels found in BME cells, none of the endothelial cell types studied expressed appreciable levels of An g1 or Ang2 mRNAs, whereas smooth muscle cells expressed both Ang1 and Ang2. BME cell Ang2 mRNA levels were increased by vascular endothelial growth factor (1.9- to 2.9-fold), basic fibroblast growth factor (1.6 - to 2-fold), both cytokines in combination (2.9- to 4-fold), and hypo xia (3.1- to 5.6-fold) and were decreased by Ang1 (31% to 70%) or tran sforming growth factor-beta(1) (64% to 81%). Ang2 also decreased (60% to 82%) BME cell Ang2 mRNA. mRNA levels for the Tie1 or Tie2 receptors were only slightly modulated under the conditions described above. Th ese findings suggest that the angiogenic effect of a number of regulat ors may be achieved in part through the regulation of an autocrine loo p of Ang2 activity in microvascular endothelial cells.