Oleic acid and adipokines synergize in inducing proliferation and inflammatory signalling in human vascular smooth muscle cells.
Bottom Line: CM itself does not contain fatty acids, but CM in combination with OA markedly enhances proliferation of hVSMC in a synergistic way.Both the nuclear factor (NF)-κB and the mammalian target of rapamycin (mTOR) pathway were synergistically activated under these conditions and found to be essential for hVSMC proliferation.Expression of iNOS and production of nitric oxide were only enhanced under these conditions and were paralleled by a marked release of VEGF.
Affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.Show MeSH
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Mentions: We determined iNOS expression in hVSMC after incubation with CM, OA and CMOA for 24 hrs (Fig. 6A). CM and OA treatment had no significant effect on iNOS expression. However, the combination of both induced a 2.3-fold increase of iNOS expression in SMC. It is well established that an increased iNOS expression leads to an enhanced VEGF production in different cell types [18–20]. CM alone contains 122 ± 6 pg/ml VEGF (n = 16). Both CM and OA increased VEGF concentration in SMC medium 2.1- and 2.3-fold, respectively, taking into account the endogenous VEGF content of CM (Fig. 6B). In addition, CMOA increased VEGF concentration in a synergistic manner (5.5-fold). Concomitantly, a significant increase in nitric oxide production by 1.5-fold was observed in hVSMC after incubation with the combination CMOA (Fig. 6C). VEGF treatment showed a significant effect (2.5-fold) on proliferation and the combination of VEGF and OA markedly enhanced the proliferation in an additive way (5-fold) (Fig. 6D). Inhibition of NOS by L-nitro-l-arginine methyl ester (NAME) had no effect on the proliferation induced by CM and OA alone, yet it completely abolished the synergistic effect of the two stimuli. Notably, an additive proliferative effect of CM and OA was still observed (Fig. 6E).
Affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.