Article
Systemic anti-VEGF actions
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Published: | June 15, 2011 |
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VEGF is a central endothelial and angiogenic peptide growth factor. In the past 2 decades, various functions of VEGF (generally referred to as VEGF-A165) and its relatives (VEGF-B, VEGF-C, VEGF-D, VEGF-E, PlGF-1, PlGF-2) and their central importance for different aspects of endothelial function have been described and characterized. All possible side effect of therapeutic VEGF inhibition can be explained by the inhibition of VEGF action.VEGF actions on the endothelium are: stimulation of migration, stimulation of proliferation, anti-hrombotic action, anti-apoptotic action, anti-proliferative for smooth muscle cells secondary to the release of nitric oxide (NO) and prostacyclin (PGI2), regulation of permeability, release of endothelial cells from the bone marrow and stimulation of their ability to home at sites of endothelial repair. Based on these actions of VEGF, possible side effects of anti-VEGF treatment are: endothelial dysfunction, arterial hypertension and blood pressure crises, vascular regression, capillary bleeding, atherosclerotic plaque rupture triggering ischemic complications such as myocardial infarction or stroke. Taken together, the therapeutic inhibition of VEGF action can lead to multiple and relevant important systemic side effects based on fundamental involvement of VEGF in endothelial physiology.