Endothelial cells (ECs) and smooth muscle cell (SMC) play a key part during development of fibrosis in the intima being partly responsible for synthesis of matrix metalloproteinase (MMPs) and various regulators and substrates of these enzymes. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) consumption, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has beneficial effects on atherosclerosis but its effect on the development of fibrosis is relatively unknown. <i>Objective:</i> Determine the effects of EPA and DHA, alone or in combination, on fibrosis-related factors in aortic SMCs (AoSMCs) and human umbilical vein ECs (HUVECs) and human aortic ECs (HAECs). <i>Results:</i> Treatment of cells with/without 10 μM DHA, EPA, oleic acid (OA) or vehicle control (VC) altered expression of MMPs, regulators and substrates of MMPs and inflammatory cytokines. EPA increased the α-actin:β-actin ratio indicative of a more contractile SMC phenotype and gelatinase (MMP-2 and -9) activity in HUVECs. In aortic cells, EPA and DHA decreased uPAR mRNA and protein expressions. DHA, EPA and DHA: EPA (at 3:1 and 1:1) decreased SMC migration, this did not involve uPA/plasmin activity. <i>Conclusion:</i> EPA and DHA could decrease inflammatory cytokines and the fibrogenic environment in atherosclerotic lesions by decreasing MMP expression and activity. These fatty acids may also reduce SMC migration and proliferation, independently of uPA/plasmin activity, potentially reducing SMC build up in the intima. This could possibly prevent and/or show plaque progression and increase the stability of advanced plaques.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499741 |
| Date | January 2009 |
| Creators | Whyte, Claire Susan |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25877 |
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