Heart Disease Weekly

Research on angiogenesis described by scientists at University of Texas

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"Am J Physiol Cell Physiol 296: C1162-C1170, 2009. First published February 25, 2009; doi:10.1152/ajpcell.00533.2008.-Coronary artery disease results in progressive vascular stenosis associated with chronic myocardial ischemia. Vascular endothelial growth factor (VEGF) stimulates endothelial cell angiogenic responses to revascularize ischemic tissues; however, the effect of chronic hypoxia on the responsiveness of endothelial cells to VEGF remains unclear. We, therefore, investigated whether hypoxia alters VEGF-stimulated signaling and angiogenic responses in primary human coronary artery endothelial (HCAE) cells. Exposure of HCAE cells to hypoxia (1% O-2) for 24 h decreased VEGF-stimulated endothelial cell migration (similar to 82%), proliferation (similar to 30%), and tube formation. Hypoxia attenuated VEGF-stimulated activation of endothelial nitric oxide (NO) synthase (eNOS) (similar to 72%) and reduced NO production in VEGF-stimulated cells from 237 +/- 38.8 to 61.3 +/- 28.4 nmol/l. Moreover, hypoxia also decreased the ratio of phosphorylated eNOS to total eNOS in VEGF-stimulated cells by similar to 50%. This effect was not observed in thrombin-stimulated cells, suggesting that hypoxia specifically inhibited VEGF signaling upstream of eNOS phosphorylation. VEGF-induced activation of Akt, ERK1/2, p38, p70S6 kinases, and S6 ribosomal protein was also attenuated in hypoxic cells. Moreover, VEGF-stimulated phosphorylation of VEGF receptor-2 (KDR) at Y996 and Y1175 was decreased by hypoxia. This decrease correlated with a 70 +/- 12% decrease in KDR protein expression. Analysis of mRNA from these cells showed that hypoxia reduced steady-state levels of KDR mRNA by 52 +/- 16% and decreased mRNA stability relative to normoxic cells. Our findings demonstrate that chronic hypoxia attenuates VEGF-stimulated signaling in HCAE cells by specific downregulation of KDR expression," wrote B. Olszewskapazdrak and colleagues, University of Texas.

The researchers concluded: "These data provide a novel explanation for the impaired angiogenic responses to VEGF in endothelial cells exposed to chronic hypoxia.."

Olszewskapazdrak and colleagues published their study in American Journal of Physiology - Cell Physiology (Chronic hypoxia attenuates VEGF signaling and angiogenic responses by downregulation of KDR in human endothelial cells. American Journal of Physiology - Cell Physiology, 2009;296(5):C1162-C1170).

For more information, contact D.H. Carney, University of Texas Med Branch, Dept. of Biochemistry & Molecular Biology, 301 University Blvd., Galveston, TX 77555, USA.

Publisher contact information for the American Journal of Physiology - Cell Physiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.

Keywords: United States, Galveston, Angiogenesis, Angiology, Cardiology, Coronary Artery Disease, Drugs, Enzyme Research, Heart Disease, Ischemia, Myocardial Ischemia, Nitric Oxide, Oncology, Pharmaceuticals, Physiology, Stenosis, Synthase, Therapy, Treatment, Tumor Vascularization, VEGF, Vascular Endothelial Growth Factor, University of Texas.

This article was prepared by Heart Disease Weekly editors from staff and other reports. Copyright 2009, Heart Disease Weekly via NewsRx.com.