title: Microvascular endothelial cells differ in basal and hypoxia-regulated expression of angiogenic factors and their receptors.
abstract: Phenotypically and functionally different types of microvascular endothelial cells (MVECs) derived from the developing corpus luteum were isolated and characterized by our group. We investigated whether these cytokeratin-positive (CK+) and cytokeratin-negative (CK-) MVECs differed in the expression of angiogenic factors and their regulation under hypoxia. Using quantitative RT-PCR, VEGF and its receptors, Flk-1 and Flt-1, were detected in CK- MVECs. The mRNA expression of Flk-1 mRNA was 100 times as high as that of Flt-1 mRNA. CK+ MVECs expressed VEGF and Flt-1 mRNA, but were devoid of Flk-1 transcripts. No Ang-1 mRNA was demonstrated in either cell type, and Ang-2 mRNA was found only in CK- MVECs. Tie-2 mRNA was detected in both MVEC types, but levels were 150 times as high in CK- MVECs as in CK+ MVECs. mRNA of hypoxia-inducible factors Hif-1alpha and Hif-1beta was expressed in both MVEC types. After hypoxia, neither VEGF, nor Flk-1, nor Tie-2 mRNA expression was altered in either MVEC type. Flt-1 expression and Ang-2 mRNA expression were significantly increased at about 2.5-fold (P < 0.05) in CK- MVECs, but not in CK+ MVECs. Our study demonstrates the varying expression and regulation of angiogenesis-related factors and receptors in phenotypically different MVEC types.
authors.affiliation: Institute of Anatomy, Institute of Pharmacy, University of Leipzig, Liebigstrasse 13, Germany.
authors.forename: Gerelsul
authors.initials: G
authors.lastname: Tscheudschilsuren
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aust
authors.forename: Karen
authors.initials: K
authors.lastname: Nieber
authors.forename: Nicole
authors.initials: N
authors.lastname: Schilling
authors.forename: Katharina
authors.initials: K
authors.lastname: Spanel-Borowski
mesh_terms: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001667:Binding, Competitive; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003338:Corpus Luteum / Q000196:embryology; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006801:Humans; D000860:Hypoxia; D007633:Keratins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009389:Neovascularization, Pathologic; D010641:Phenotype; D010766:Phosphorylation; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D042787:Receptor, TIE-2; D018336:Receptors, Aryl Hydrocarbon; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1; D051941:fms-Like Tyrosine Kinase 3
chemical_list: C497396:ARNT protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D014443:Tyrosine; D012313:RNA; D007633:Keratins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D051941:fms-Like Tyrosine Kinase 3