A Snake Venom-Secreted Phospholipase A₂ Induces Foam Cell Formation Depending on the Activation of Factors Involved in Lipid Homeostasis

Figure 8

Schematic illustration of the mechanisms involved in foam cell formation induced by MT-III a GIIA snake venom sPLA₂. (1) MT-III by acting on cellular membrane of macrophages generates free fatty acids, which will be internalized by CD36 scavenger receptors; (2) activation of C36 receptor leads to formation of (3) lipid droplets and (4) expression of COX-2. (5) MT-III induces production of 15-d-PGJ₂ via COX-1 pathway (6). This mediator and free fatty acids activate the cytoplasmic transcription factors PPARs; (7) PLIN2, scaffold protein for lipid droplet assembly, is under transcriptional control of PPAR-β/δ and favors the increase of (8) lipid droplet formation. (9) Both PPAR-γ and PPAR-β/δ upregulate CD36 protein expression forming a positive loop for generation of lipid droplets in macrophages. (10) MT-III also activates endoplasmic reticulum enzymes (DGAT and ACAT) crucial for formation of lipid droplets.