Premium
Effect of PUFAs on extracellular matrix production and remodeling in vascular smooth muscle cell cultures in an atherosclerotic model
Author(s) -
PalominoMorales Rogelio,
Alejandre M. Jose,
Perales Sonia,
Torres Carolina,
Linares Ana
Publication year - 2014
Publication title -
european journal of lipid science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.614
H-Index - 94
eISSN - 1438-9312
pISSN - 1438-7697
DOI - 10.1002/ejlt.201400141
Subject(s) - rhoa , microbiology and biotechnology , extracellular matrix , fibronectin , gene expression , biology , vascular smooth muscle , chemistry , biochemistry , signal transduction , endocrinology , gene , smooth muscle
The aim of this study was to investigate the molecular mechanisms underlying the anti‐atherosclerotic effects of PUFA. We hypothesized that, besides their lipid lowering and plaque stabilizing properties, PUFA may exert direct effects on cholesterol homeostasis and on the production and remodeling of extracellular matrix proteins in vascular smooth‐muscle cells, altering their gene expression. Collagen synthesis, expression of genes for collagen types I, II, and III, and [H 3 ]‐mevalonate incorporation to proteins were higher in smooth‐muscle cells cultures obtained from cholesterol‐fed chicks than in cultures from chicks on standard diet and these increases were reversed by PUFA treatment. Eicosapentaenoic, docosahexaenoic, and AAs decreased col2α1 , col3α1 , fibronectin , and mmp2 gene expression, inhibited RhoA activation, [H 3 ]‐mevalonate incorporation into isoprenylated proteins and srebp‐1 gene expression, also inducing pparγ gene expression. Practical applications: Consumption of PUFA is considered a source of health benefits. This work provides information about the different mechanisms through which PUFA may exert their anti‐atherogenic effects, especially those related to extracellular matrix production and remodeling. PPARγ, RhoA, and protein isoprenylation may contribute to the molecular mechanisms underlying these effects. Two of the most widely known properties of PUFA contributing to their anti‐atherosclerotic effects are their lipid lowering and plaque stability properties. Here, we propose two more mechanisms regarding cholesterol homeostasis and production and remodeling of extracellular matrix proteins in vascular smooth‐muscle cells. Considering the first one, we have demonstrated an induction of the transcription factor pparγ gene together with an inhibition of the srebp‐1 gene. Considering the last one we have assessed effects both at gene level and affecting RhoA activation.