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Open AccessArticle

A Secreted Phospholipase A2 Induces Formation of Smooth Muscle Foam Cells Which Transdifferentiate to Macrophage-Like State

Pharmacology Laboratory, Butantan Institute, 05503-900 São Paulo, Brazil
Department of Cardiology and Angiology, Internal medicine, Otto-von-Guericke-Universität Magdeburg, 39120 Magdeburg, Germany
Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, 01246-903 São Paulo, Brazil
Instituto Clodomiro Picado Institute, University of Costa Rica, 11501 San José, Costa Rica
Author to whom correspondence should be addressed.
Molecules 2019, 24(18), 3244;
Received: 18 July 2019 / Revised: 30 August 2019 / Accepted: 2 September 2019 / Published: 6 September 2019
(This article belongs to the Section Natural Products Chemistry)
Vascular smooth muscle cells (VSMCs) loaded with lipid droplets (LDs) are markers of atherosclerosis. In this disease, inflammatory Group IIA-secreted phospholipase A2s (GIIA sPLA2s) are highly expressed in VSMCs, but their actions in these cells are unknown. Here, we investigated the ability of myotoxin III (MT-III), an ophidian GIIA sPLA2 sharing structural and functional features with mammalian GIIA sPLA2s, to induce LD formation and lipid metabolism factors involved in this effect. Modulation of VSMC phenotypes by this sPLA2 was also evaluated. Incubation of VSMCs with MT-III significantly increased the number of LDs. MT-III upregulated scavenger receptor type 1 (SR-A1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein expression and enhanced acetylated-low density lipoprotein (acLDL) uptake by VSMCs, revealing the ability of a GIIA PLA2 to modulate scavenger receptor activities. MT-III induced translocation and protein expression of PPAR-γ and -β/δ. Inhibition of peroxisome proliferator-activated receptors (PPARs) and diacylglycerol O-acyltransferase (DGAT) and acyl-CoA:cholesterolacyltransferase (ACAT) enzymes abrogated MT-III-induced LD formation. Moreover, in response to MT-III, VSMCs acquired phagocytic activity and expressed macrophage markers CD68 and MAC-2. In conclusion, MT-III is able to stimulate VSMCs and recruit factors involved in lipid uptake and metabolism, leading to the formation of VSMC-derived foam cells with acquisition of macrophage-like markers and functions. View Full-Text
Keywords: phospholipase A2; vascular smooth muscle cells; lipid droplets phospholipase A2; vascular smooth muscle cells; lipid droplets
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Giannotti, K.C.; Weinert, S.; Viana, M.N.; Leiguez, E.; Araujo, T.L.S.; Laurindo, F.R.M.; Lomonte, B.; Braun-Dullaeus, R.; Teixeira, C. A Secreted Phospholipase A2 Induces Formation of Smooth Muscle Foam Cells Which Transdifferentiate to Macrophage-Like State. Molecules 2019, 24, 3244.

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