Senior Scholars Program

Title

Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension

Date

6-25-1998

Document Type

Article

Medical Subject Headings

Animals; Anoxia; Blotting, Northern; Capillary Permeability; Endothelial Growth Factors; Hypertension, Pulmonary; Immunohistochemistry; In Situ Hybridization; Lung; Lymphokines; Male; Pulmonary Alveoli; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Vascular endothelial growth factor (VEGF) is a potent mitogenic and permeability factor targeting predominantly endothelial cells. At least two tyrosine kinase receptors, Flk-1 and Flt-1, mediate its action and are mostly expressed by endothelial cells. VEGF and VEGF receptor expression are upregulated by hypoxia in vivo and the role of VEGF in hypoxia-induced angiogenesis has been extensively studied in a variety of disease entities. Although VEGF and its receptors are abundantly expressed in the lung, their role in hypoxic pulmonary hypertension and the accompanying vascular remodeling are incompletely understood. We report in this in vivo study that hypoxia increases mRNA levels for both VEGF and Flk-1 in the rat lung. The kinetics of the hypoxic response differ between receptor and ligand: Flk-1 mRNA showed a biphasic response to hypoxia with a significant, but transient, rise in mRNA levels observed after 9-15 h of hypoxic exposure and the highest levels noted after 3 wk. In contrast, VEGF mRNA levels did not show a significant increase with acute hypoxia, but increased progressively after 1-3 wk of hypoxia. By in situ hybridization, VEGF mRNA was localized predominantly in alveolar epithelial cells with increased signal in the lungs of hypoxic animals compared with controls. Immunohistochemical staining with anti-VEGF antibodies localized VEGF peptide throughout the lung parenchyma and was increased in hypoxic compared with normoxic animals. Furthermore, hypoxic animals had significantly higher circulating VEGF concentrations compared with normoxic controls. Lung vascular permeability as measured by extravasation of Evans Blue dye was not significantly different between normoxic and hypoxic animals, although a tendency for increased permeability was seen in the hypoxic animals. These findings suggest a possible role for VEGF in the pulmonary response to hypoxia.

Rights and Permissions

Citation: Am J Respir Cell Mol Biol. 1998 Jun;18(6):768-76.

Related Resources

Link to Article in PubMed

Comments

Medical student Victoria Arthur participated in this study as part of the Senior Scholars research program.

PubMed ID

9618381