Study on the effects of MT-III, a snake venom secreted phospholipase A2 (sPLA2), on isolated rat and human aortic vascular smooth muscle cells: Dedifferentiation into a phagocytic active macrophage-like phenotype
Phospholipases A2 (PLA2s) are abundant in snake venoms and have been widely employed as pharmacological tools to investigate the role of this class of enzymes in diverse pathophysiological processes. MT-III, an Asp49 PLA2 isolated from Bothrops asper snake venom is classified into the group IIA sPLA2s. Mammalian GIIA-PLA2s are highly expressed in vascular smooth muscle cells (VSMCs) and their synthesis is stimulated by inflammatory cytokines, such as TNF-1alpha, IL-6 and IL-1. Recently, we have demonstrated that MT-III is able to induce increase in lipid droplet numbers in VSMCs and to elicit diverse factors of lipid metabolism involved in formation of foam cells. Literature shows that aortic VSMC loaded with cholesterol can assume the appearance and functions of macrophage foam cells, evidenced by a marked decline in the expression of genes related to the contractile phenotype, such as alpha-actin and smooth muscle myosin heavy chain, and increased expression of macrophage markers, such as CD68, MAC2 and CD163 molecules.Moreover, these cells were shown to be able to display macrophage functions, which include increased phagocytotic activity. However, the contribution of sPLA2s to the differentiation of VSMCs into macrophage-like cells, during vascular inflammatory processes is still unknown. This study will investigate the potential role of PLA2s during the process of VSMCs phenotype switch and will help to undestand the phenomenon and underlying molecular mechanisms.
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