| Autor: |
Giannotti KC; Pharmacology Laboratory, Butantan Institute, 05503-900 São Paulo, Brazil. karina.giannotti@butantan.gov.br., Weinert S; Department of Cardiology and Angiology, Internal medicine, Otto-von-Guericke-Universität Magdeburg, 39120 Magdeburg, Germany. soenke.weinert@med.ovgu.de., Viana MN; Pharmacology Laboratory, Butantan Institute, 05503-900 São Paulo, Brazil., Leiguez E; Pharmacology Laboratory, Butantan Institute, 05503-900 São Paulo, Brazil. elbio.junior@butantan.gov.br., Araujo TLS; Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, 01246-903 São Paulo, Brazil. tlarissa2006@gmail.com., Laurindo FRM; Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, 01246-903 São Paulo, Brazil. francisco.laurindo@incor.usp.br., Lomonte B; Instituto Clodomiro Picado Institute, University of Costa Rica, 11501 San José, Costa Rica. BRUNO.LOMONTE@ucr.ac.cr., Braun-Dullaeus R; Department of Cardiology and Angiology, Internal medicine, Otto-von-Guericke-Universität Magdeburg, 39120 Magdeburg, Germany. r.braun-dullaeus@med.ovgu.de., Teixeira C; Pharmacology Laboratory, Butantan Institute, 05503-900 São Paulo, Brazil. catarina.teixeira@butantan.gov.br. |
| Abstrakt: |
Vascular smooth muscle cells (VSMCs) loaded with lipid droplets (LDs) are markers of atherosclerosis. In this disease, inflammatory Group IIA-secreted phospholipase A 2 s (GIIA sPLA 2 s) 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 sPLA 2 sharing structural and functional features with mammalian GIIA sPLA 2 s, to induce LD formation and lipid metabolism factors involved in this effect. Modulation of VSMC phenotypes by this sPLA 2 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 PLA 2 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. |
