RRC ID 38776
Author Nomura M, Yamagishi S, Harada S, Hayashi Y, Yamashima T, Yamashita J, Yamamoto H.
Title Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes.
Journal J Biol Chem
Abstract Hypoxia is the principal factor that causes angiogenesis. These experiments were conducted to explore how it induces the proliferation of vascular cells, a key step in angiogenesis. Human umbilical vein endothelial cells and bovine retinal pericytes were grown in controlled atmosphere culture chambers containing various concentrations of oxygen. The numbers of both endothelial cells and pericytes increased significantly under hypoxic conditions; the O2 concentrations that achieved maximal growth promotion were 10% for endothelial cells and 2.5% for pericytes. Quantitative reverse transcription-polymerase chain reaction analysis revealed that mRNAs coding for the secretory forms of vascular endothelial growth factor (VEGF), a mitogen specific to endothelial cells, were present in both endothelial cells and pericytes and that their levels increased significantly in the two cell types as the atmospheric O2 concentration decreased. The two genes for VEGF receptors, kinase insert domain-containing receptor (kdr) and fms-like tyrosine kinase 1 (flt1), were found to be constitutively expressed in endothelial cells, and their relative mRNA levels were ranked in that order. On the other hand, only flt1 mRNA was detected in pericytes under hypoxic conditions. Furthermore, most antisense oligodeoxyribonucleotides complementary to VEGF mRNAs efficiently inhibited DNA synthesis in endothelial cells cultured under hypoxic conditions. These results indicate that autocrine and paracrine VEGFs may take part in the hypoxia-induced proliferation of endothelial cells.
Volume 270(47)
Pages 28316-24
Published 1995-11-24
DOI 10.1074/jbc.270.47.28316
PII S0021-9258(18)87932-7
PMID 7499331
MeSH Animals Base Sequence Cattle Cell Division / drug effects Cell Division / physiology Cell Hypoxia Cells, Cultured DNA / antagonists & inhibitors DNA / biosynthesis DNA Primers DNA Replication / drug effects Endothelial Growth Factors / biosynthesis Endothelial Growth Factors / physiology* Endothelium, Vascular / cytology* Endothelium, Vascular / drug effects Endothelium, Vascular / physiology* Humans Kinetics Lymphokines / biosynthesis Lymphokines / physiology* Microcirculation Molecular Sequence Data Muscle, Smooth, Vascular / cytology Muscle, Smooth, Vascular / drug effects Muscle, Smooth, Vascular / physiology* Oligonucleotide Probes Oligonucleotides, Antisense / pharmacology Polymerase Chain Reaction Proto-Oncogene Proteins / biosynthesis RNA, Messenger / biosynthesis Receptor Protein-Tyrosine Kinases / biosynthesis* Receptors, Growth Factor / biosynthesis* Receptors, Mitogen / biosynthesis Receptors, Vascular Endothelial Growth Factor Retina Retinal Vessels Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factors
IF 4.238
Times Cited 283
Human and Animal Cells U251(RCB0461)