Related Experiment Videos
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis
H F Dvorak1, L F Brown, M Detmar
1Department of Pathology, Beth Israel Hospital, Boston, Massachusetts.
The American Journal of Pathology
|May 1, 1995
Summary
Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by increasing blood vessel permeability and stimulating cell growth. Tumors may exploit this mechanism, but how other angiogenic factors induce leaky vessels remains a paradox, possibly via VEGF induction.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Vascular Endothelial Growth Factor (VEGF) is a key cytokine in angiogenesis, driving endothelial cell (EC) proliferation and migration.
- VEGF also induces microvascular hyperpermeability, leading to plasma protein extravasation and fibrin gel formation, which supports new vessel ingrowth.
- This process is observed in tumors, non-neoplastic pathology, and physiological angiogenesis, suggesting a conserved mechanism.
Purpose of the Study:
- To elucidate the role of VEGF in angiogenesis, particularly its dual function in stimulating ECs and increasing vascular permeability.
- To investigate the paradox of how angiogenic factors other than VEGF induce hyperpermeable new vessels.
- To explore potential mechanisms by which other angiogenic factors might indirectly promote angiogenesis.
Main Methods:
- Review and synthesis of existing literature on VEGF, angiogenesis, and vascular permeability.
- Analysis of the mechanisms by which VEGF affects endothelial cells and the extracellular matrix.
- Examination of the role of other angiogenic factors, such as TGF-alpha, in relation to VEGF expression.
Main Results:
- VEGF directly stimulates ECs and indirectly promotes angiogenesis by increasing vascular permeability and creating a provisional matrix.
- Tumors and pathological conditions utilize these fundamental mechanisms of angiogenesis.
- A paradox exists where non-VEGF angiogenic factors induce hyperpermeable vessels, potentially by upregulating VEGF expression.
Conclusions:
- VEGF's induction of vascular hyperpermeability is a critical, possibly essential, component of angiogenesis.
- The mechanism by which non-VEGF angiogenic factors induce leaky vessels is not fully understood but may involve stimulating VEGF expression.
- Transforming Growth Factor-alpha (TGF-alpha) is presented as an example that upregulates VEGF, suggesting a potential pathway for angiogenesis induction in tumors.