Effect of PUFAs on extracellular matrix production and remodeling in vascular smooth muscle cell cultures in an atherosclerotic model.

Palomino‐Morales, Rogelio; Alejandre, M. Jose; Perales, Sonia; Torres, Carolina; Linares, Ana

The aim of this study was to investigate the molecular mechanisms underlying the anti-atherosclerotic effects of PUFF. We hypothesized that, besides their lipid lowering and plaque stabilizing properties, PUFF 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 [H3]-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 PUFF treatment. Eicosapentaenoic, docosahexaenoic, and AAs decreased col2α1, col3α1, fibronectin, and mmp2 gene expression, inhibited RhoA activation, [H3]-mevalonate incorporation into isoprenylated proteins and srebp-1 gene expression, also inducing pparg gene expression. Practical applications: Consumption of PUFF is considered a source of health benefits. This work provides information about the different mechanisms through which PUFF may exert their antiatherogenic effects, especially those related to extracellular matrix production and remodeling. PPARγ, RhoA, and protein isoprenylation may contribute to the molecular mechanisms underlying these effects.

UNSATURATED fatty acids; ATHEROSCLEROSIS treatment; GENE expression; EXTRACELLULAR matrix; SMOOTH muscle; MUSCLE cells; HOMEOSTASIS; EICOSAPENTAENOIC acid

European Journal of Lipid Science & Technology, 2014, Vol 116, Issue 11, p1485

1438-7697

Academic Journal

10.1002/ejlt.201400141