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

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 col2 alpha 1, col3 alpha 1, fibronectin, and mmp2 gene expression, inhibited RhoA activation, [H-3]-mevalonate incorporation into isoprenylated proteins and srebp-1 gene expression, also inducing ppar gamma 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. PPAR gamma, RhoA, and protein isoprenylation may contribute to the molecular mechanisms underlying these effects.