Figure 1- Angiogenesis
Figure 1- Angiogenesis - New blood vessels are formed in response to various physiological and/or pathological stimuli, of which hypoxia, is one of the most relevant.
Hypoxia activates multiple cellular response cascades, with special emphasis on activation of extracellular matrix metalloproteases and increased synthesis and release of growth factors, including VEGF.
The latter acts on membrane receptors, activating intracellular enzyme pathways through intracellular signalling, which results in response amplification.
This ultimately leads to cellular proliferation, migration and differentiation, with formation of new blood vessels.
Different drug categories act on different stages of the neovascularization process(6).
Joint action on various cascade levels should theoretically lead to an increase in treatment effect and/or a decrease in the effective dose and/or a more prolonged effect.