Figure 8.

Mechanism of FA-mediated stimulation of EC angiogenic function via CD36. Increased FA uptake results in binding of these molecules to PPARs at the surface of the nucleus. In turn, PPARs translocate and dimerize with the nuclear receptor RXR resulting in the modulation of CD36 gene transcription. Functionally, FA uptake through the CD36 receptor results in the upregulation of mitochondrial Cpt1a and activation of AMPKα, which in turn increases VEGF and eNOS expression in ECs under ischemic conditions. This increase in angiogenic factors promotes EC recruitment, migration, invasion and the formation of new vessels in muscle tissues during post-ischemic recovery. On the other hand, insulin receptor (IR) actions are modulated in a CD36-dependent manner preventing src-mediated phosphorylation leading to reduced PI3K/Akt signaling, which results in decreased VEGF and angiogenesis in ECs [38,39].