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The effects of platelet-derived growth factor in cultured microvessel endothelial cells
1Department of Medicine, Veterans Administration Medical Center, Iowa City, Iowa 52246.
Abstract:
The effects of platelet-derived growth factor (PDGF) on thymidine incorporation into DNA and glucose and neutral amino acid uptake were studied in endothelial cells cultured from macrovessels (bovine aorta and pulmonary artery) and microvessels (bovine fat and mouse brain). Similar to previous studies, PDGF did not bind to macrovessel cells, nor did it influence their metabolic function. In contrast, PDGF bound specifically to the two types of microvessel cell culture and in these cells also stimulated the uptake of glucose and neutral amino acids as well as the incorporation of thymidine into DNA. Stimulatory effects of PDGF occurred at concentrations of 2 ng/ml, with maximal stimulation up to 5-fold of the control value for amino isobutyric acid and glucose uptake and up to 8- to 10-fold for thymidine incorporation. The maximal effects of PDGF were additive to those of insulin-like growth factor, I, a known stimulator of all three metabolic processes in microvessel endothelial cells. The binding of PDGF to the endothelial cells was, in general, equivalent to PDGF binding to human foreskin fibroblasts, both in the magnitude of tracer binding and in the affinity of binding. Similar effects were found with recombinant and platelet-derived PDGF. We conclude that these two cultured microvessel endothelial cells not only produce PDGF-like material, but are capable of binding and responding to PDGF.
Insights
Platelet-derived growth factor (PDGF) specifically binds to and stimulates metabolic activity in microvessel endothelial cells, but not macrovessel cells. This suggests a key role for PDGF in microvascular function.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant.
- Endothelial cells form the inner lining of blood vessels and play critical roles in vascular homeostasis and disease.
Purpose of the Study:
- To investigate the differential effects of PDGF on macrovessel and microvessel endothelial cells.
- To determine PDGF's impact on DNA synthesis, glucose uptake, and amino acid uptake in various endothelial cell types.
Main Methods:
- Cultured endothelial cells from bovine aorta, pulmonary artery (macrovessels), and bovine fat, mouse brain (microvessels).
- Assessed PDGF binding, thymidine incorporation into DNA, and uptake of glucose and neutral amino acids.
- Utilized both native and recombinant PDGF.
Main Results:
- PDGF did not bind to or affect macrovessel endothelial cells.
- PDGF specifically bound to and stimulated thymidine incorporation, glucose uptake, and neutral amino acid uptake in microvessel endothelial cells.
- Stimulatory effects were observed at 2 ng/ml PDGF, with maximal increases up to 5-fold for uptake and 8-10 fold for DNA incorporation.
- PDGF effects were additive to insulin-like growth factor I.
- PDGF binding to microvessel cells was comparable to human foreskin fibroblasts.
Conclusions:
- Cultured microvessel endothelial cells can bind and respond to PDGF.
- Microvessel endothelial cells may produce PDGF-like material, indicating an autocrine or paracrine signaling role.
- These findings highlight a specific functional role for PDGF in microvascular endothelial cells distinct from macrovascular cells.