Oleic Acid and Adipokines Synergize in Inducing Proliferation and Inflammatory Signalling in Human Vascular Smooth Muscle Cells

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2010 Jun 4

PMID 20518853

Citations 26

Authors

Daniela Lamers

Raphaela Schlich

Sabrina Greulich

Shlomo Sasson

Henrike Sell

Jurgen Eckel

Affiliations

Soon will be listed here.

Abstract

In the context of obesity, perivascular fat produces various adipokines and releases free fatty acids, which may induce inflammation and proliferation in the vascular wall. In this study we investigated how adipokines, oleic acid (OA) and the combined treatment regulate human vascular smooth muscle cell (hVSMC) proliferation and migration and the underlying signalling pathways. Adipocyte-conditioned media (CM) generated from human adipocytes induces a prominent proliferation and migration of hVSMC. Autocrine action of adiponectin totally abolishes CM-induced proliferation. Furthermore, OA but not palmitic acid induces proliferation of hVSMC. 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 was only enhanced by combined treatment inducing a marked release of VEGF. Combination of OA and VEGF induces an additive increase of hVSMC proliferation. We could show that the combination of CM and OA led to a synergistic proliferation of hVSMC. Expression of iNOS and production of nitric oxide were only enhanced under these conditions and were paralleled by a marked release of VEGF. These results suggest that the combined elevated release of fatty acids and adipokines by adipose tissue in obesity might be critically related to hVSMC dysfunction, vascular inflammation and the development of atherosclerosis.

Citing Articles

Independent and Interactive Roles of Immunity and Metabolism in Aortic Dissection.

Li S, Li J, Cheng W, He W, Dai S Int J Mol Sci. 2023; 24(21).

PMID: 37958896 PMC: 10647240. DOI: 10.3390/ijms242115908.

Adipose Tissue Paracrine-, Autocrine-, and Matrix-Dependent Signaling during the Development and Progression of Obesity.

Johnston E, Abbott R Cells. 2023; 12(3).

PMID: 36766750 PMC: 9913478. DOI: 10.3390/cells12030407.

Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid.

Santa-Maria C, Lopez-Enriquez S, Montserrat-de la Paz S, Geniz I, Reyes-Quiroz M, Moreno M Nutrients. 2023; 15(1).

PMID: 36615882 PMC: 9824542. DOI: 10.3390/nu15010224.

Physiological Doses of Oleic and Palmitic Acids Protect Human Endothelial Cells from Oxidative Stress.

Palomino O, Giordani V, Chowen J, Alfonso S, Goya L Molecules. 2022; 27(16).

PMID: 36014457 PMC: 9415781. DOI: 10.3390/molecules27165217.

Expression of miRNAs Targeting ATP Binding Cassette Transporter 1 (ABCA1) among Patients with Significant Carotid Artery Stenosis.

Jeong S, Jun J, Kim J, Park H, Cho Y, Kim G Biomedicines. 2021; 9(8).

PMID: 34440128 PMC: 8406092. DOI: 10.3390/biomedicines9080920.

References

Lu G, Meier K, Jaffa A, Rosenzweig S, Egan B . Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular smooth muscle cells. Hypertension. 1998; 31(4):978-85. DOI: 10.1161/01.hyp.31.4.978. View

Fang I, Yang C, Yang C, Chen M . Comparative effects of fatty acids on proinflammatory gene cyclooxygenase 2 and inducible nitric oxide synthase expression in retinal pigment epithelial cells. Mol Nutr Food Res. 2009; 53(6):739-50. DOI: 10.1002/mnfr.200800220. View

Hu F, Willett W, Li T, Stampfer M, Colditz G, Manson J . Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med. 2004; 351(26):2694-703. DOI: 10.1056/NEJMoa042135. View

Li L, Mamputu J, Wiernsperger N, Renier G . Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes. 2005; 54(7):2227-34. DOI: 10.2337/diabetes.54.7.2227. View

Minhajuddin M, Bijli K, Fazal F, Sassano A, Nakayama K, Hay N . Protein kinase C-delta and phosphatidylinositol 3-kinase/Akt activate mammalian target of rapamycin to modulate NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. J Biol Chem. 2008; 284(7):4052-61. PMC: 2640976. DOI: 10.1074/jbc.M805032200. View

Aktan F . iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004; 75(6):639-53. DOI: 10.1016/j.lfs.2003.10.042. View

Ruan H, Lodish H . Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev. 2003; 14(5):447-55. DOI: 10.1016/s1359-6101(03)00052-2. View

van Dam R, Willett W, Manson J, Hu F . The relationship between overweight in adolescence and premature death in women. Ann Intern Med. 2006; 145(2):91-7. DOI: 10.7326/0003-4819-145-2-200607180-00006. View

Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y . Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999; 100(25):2473-6. DOI: 10.1161/01.cir.100.25.2473. View

10.

Hishikawa K, Oemar B, Yang Z, Luscher T . Pulsatile stretch stimulates superoxide production and activates nuclear factor-kappa B in human coronary smooth muscle. Circ Res. 1997; 81(5):797-803. DOI: 10.1161/01.res.81.5.797. View

11.

Greene E, Lu G, Zhang D, Egan B . Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration. Hypertension. 2001; 37(2):308-12. DOI: 10.1161/01.hyp.37.2.308. View

12.

Frank S, Stallmeyer B, Kampfer H, Kolb N, Pfeilschifter J . Nitric oxide triggers enhanced induction of vascular endothelial growth factor expression in cultured keratinocytes (HaCaT) and during cutaneous wound repair. FASEB J. 1999; 13(14):2002-14. View

13.

Ross R . The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362(6423):801-9. DOI: 10.1038/362801a0. View

14.

Henrichot E, Juge-Aubry C, Pernin A, Pache J, Velebit V, Dayer J . Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis?. Arterioscler Thromb Vasc Biol. 2005; 25(12):2594-9. DOI: 10.1161/01.ATV.0000188508.40052.35. View

15.

Berg A, Scherer P . Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005; 96(9):939-49. DOI: 10.1161/01.RES.0000163635.62927.34. View

16.

Artwohl M, Lindenmair A, Roden M, Waldhausl W, Freudenthaler A, Klosner G . Fatty acids induce apoptosis in human smooth muscle cells depending on chain length, saturation, and duration of exposure. Atherosclerosis. 2008; 202(2):351-62. DOI: 10.1016/j.atherosclerosis.2008.05.030. View

17.

Iacobellis G, Gao Y, Sharma A . Do cardiac and perivascular adipose tissue play a role in atherosclerosis?. Curr Diab Rep. 2008; 8(1):20-4. DOI: 10.1007/s11892-008-0005-2. View

18.

Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y . Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation. 2002; 105(24):2893-8. DOI: 10.1161/01.cir.0000018622.84402.ff. View

19.

Duplaa C, Couffinhal T, Dufourcq P, Llanas B, Moreau C, Bonnet J . The integrin very late antigen-4 is expressed in human smooth muscle cell. Involvement of alpha 4 and vascular cell adhesion molecule-1 during smooth muscle cell differentiation. Circ Res. 1997; 80(2):159-69. DOI: 10.1161/01.res.80.2.159. View

20.

Dulak J, Jozkowicz A, Dembinska-Kiec A, Guevara I, Zdzienicka A, Florek I . Nitric oxide induces the synthesis of vascular endothelial growth factor by rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2000; 20(3):659-66. DOI: 10.1161/01.atv.20.3.659. View