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European Journal of Nutrition

Published in:

01-03-2008 | ORIGINAL CONTRIBUTION

Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-κB transactivation and collagen formation in human vascular smooth muscle cells

Authors: Dr. Robert Ringseis, Susan Gahler, Klaus Eder

Published in: European Journal of Nutrition | Issue 2/2008

Abstract

Background

Atherosclerosis is characterized by extensive thickening of the arterial intima partially resulting from deposition of collagen by vascular smooth muscle cells (SMCs). Polyunsaturated fatty acids stimulate collagen formation through NF-κB activation.

Aim of the study

The present study aimed to explore the effect of conjugated linoleic acids (CLAs) which are known to inhibit NF-κB activation on collagen formation by SMCs.

Methods

Vascular SMCs were cultured with 50 µmol/l of CLA isomers (c9t11-CLA, t10c12-CLA) or linoleic acid (LA) and analysed for collagen formation and NF-κB p50 transactivation.

Results

Treatment with CLA isomers but not LA significantly reduced PDGF-stimulated [³H] proline incorporation into cell layer protein of SMCs without altering cell proliferation. Simultaneous treatment with the PPARγ inhibitor T0070907 abrogated this effect. Treatment of SMCs with c9t11-CLA and t10c12-CLA significantly reduced PDGF-induced NF-κB p50 activation.

Conclusions

CLA isomers inhibit PDGF-stimulated collagen production by vascular SMCs, which is considered to be a hallmark of atherosclerosis, in a PPARγ-dependent manner. Whether inhibition of the NF-κB-pathway is of significance for the reduction of collagen formation by CLA isomers needs further investigation.

Bowie A, O’Neill LA (2000) Oxidative stress and nuclear factor-κB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol 59:13–23CrossRef

Burke JM, Ross R (1979) Synthesis of connective tissue macromolecules by smooth muscle. Int Rev Connect Tissue Res 8:119–157

Burgess HA, Daugherty LE, Thatcher TH, Lakatos HF, Ray DM, Redonnet M, Phipps RP, Sime PJ (2005) PPARγ agonists inhibit TGF-β induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 288:L1146–L1153CrossRef

Büttner C, Skupin A, Rieber EP (2004) Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin-4: analysis of the functional collagen promoter sequences. J Cell Physiol 198:248–258CrossRef

Chen A, Zhang L, Xu J, Tang J (2002) The antioxidant (-)-epigallocatechin-3-gallate inhibits activated hepatic stellate cell growth and suppresses acetaldehyde-induced gene expression. Biochem J 368:695–704CrossRef

Chen C-N, Li Y-SJ, Yeh Y-T, Lee P-L, Usami S, Chien S, Chiu J-J (2006) Synergistic roles of platelet-derived growth factor-BB and interleukin-1β in phenotypic modulation of human aortic smooth muscle cells. PNAS 103:2665–2670CrossRef

Cheng WL, Lii CK, Chen HW, Lin TH, Liu KL (2004) Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-κB pathway. J Agric Food Chem 52:71–78CrossRef

de Winther MP, Kanters E, Kraal G, Hofker MH (2005) Nuclear factor κB signaling in atherogenesis. Arterioscler Thromb Vasc Biol 25:904–914CrossRef

Dubey R, Jackson EK, Gillespie DG, Zacharia LC, Imthurn B, Keller PJ (2000) Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity. Arterioscler Thromb Vasc Biol 20:964–972

10.

Eder K, Slomma N, Becker K (2002) Trans-10, cis-12 conjugated linoleic acid suppresses the desaturation of linoleic and α-linolenic acids in HepG2 cells. J Nutr 132:1115–1121

11.

Fu M, Zhang J, Zhu X, Myles DE, Willson TM, Liu X, Chen YE (2001) Peroxisome proliferator-activated receptor γ inhibits transforming growth factor β-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3. J Biol Chem 276:45888–45894CrossRef

12.

Hankenson KD, Watkins BA, Schoenlein IA, Allen KG, Turek JJ (2000) Omega-3 fatty acids enhance ligament fibroblast collagen formation in association with changes in interleukin-6 production. Proc Soc Exp Biol Med 223:88–95CrossRef

13.

Hwang DM, Kundu JK, Shin JW, Lee JC, Lee HJ, Surh YJ (2007) Cis-9,trans-11-Conjugated linoleic acid down-regulates phorbol ester-induced NF-κB activation and subsequent COX-2 expression in hairless mouse skin by targeting IκB kinase and PI3K-Akt. Carcinogenesis 28:363–371CrossRef

14.

Jia Y, Turek J (2005) Altered NF-nB gene expression and collagen formation induced by polyunsaturated fatty acids. J Nutr Biochem 16:500–506CrossRef

15.

Jimi S, Saku K, Uesugi N, Sakata N, Takebayashi S (1995) Oxidized low density lipoprotein stimulates collagen production in cultured arterial smooth muscle cells. Atherosclerosis 116:15–26CrossRef

16.

Katsuda S, Kaji T (2003) Atherosclerosis and extracellular matrix. J Atheroscler Thromb 10:267–274

17.

Kim JH, Hubbard NE, Ziboh V, Erickson KL (2005) Attenuation of breast tumor cell growth by conjugated linoleic acid via inhibition of 5-lipoxygenase activating protein. Biochim Biophys Acta 1736:244–250

18.

Kritchevsky D, Tepper SA, Wright S, Tso P, Czarnecki SK (2000) Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. J Am Coll Nutr 19:472S–477S

19.

Ku CH, Johnson PH, Batten P, Sarathchandra P, Chambers RC, Taylor PM, Yacoub MH, Chester AH (2006) Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch. Cardiovasc Res 71:548–556CrossRef

20.

LaPointe MC, Mendez M, Leung A, Tao Z, Yang XP (2004) Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse. Am J Physiol 286:H1416–H1424

21.

Levick SP, Loch DC, Taylor SM, Janicki JS (2007) Arachidonic acid metabolism as a potential mediator of cardiac fibrosis associated with inflammation. J Immunol 178:641–646

22.

Li M, Pascual G, Glass CK (2000) Peroxisome proliferator-activated receptor γ-dependent repression of the inducible nitric oxide synthase gene. Mol Cell Biol 20:4699–4707CrossRef

23.

Li G, Dong B, Butz DE, Park Y, Pariza MW, Cook ME (2006) NF-kappaB independent inhibition of lipopolysaccharide-induced cyclooxygenase by a conjugated linoleic acid cognate, conjugated nonadecadienoic acid. Biochim Biophys Acta 1761:969–972

24.

Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH, Roche HM (2005) Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction. J Immunol 175:4990–4998

25.

Muz MH, Deveci F, Bulut Y, Ilhan N, Yekeler H, Turgut T (2006) The effects of low dose leukotriene receptor antagonist therapy on airway remodelling and cysteinyl leukotrien expression in a mouse asthma model. Exp Mol Med 38:109–118

26.

Nieto N, Friedman SL, Greenwel P, Cederbaum AI (1999) CYP2E1-mediated oxidative stress induces collagen type I expression in rat hepatic stellate cells. Hepatology 30:987–996CrossRef

27.

Nieto N, Greenwel P, Friedman SL, Zhang F, Dannenberg AJ, Cederbaum AI (2000) Ethanol and arachidonic acid increase α 2(I) collagen expression in rat hepatic stellate cells overexpressing cytochrome P450 2E1. Role of H₂O₂ and cyclooxygenase-2. J Biol Chem 275:20136–20145CrossRef

28.

Ringseis R, Müller A, Herter C, Gahler S, Steinhart H, Eder K (2006) CLA isomers inhibit TNFα-induced eicosanoid release from human vascular smooth muscle cells via a PPARγ ligand-like action. Biochim Biophys Acta 1760:290–300

29.

Ringseis R, Gahler S, Herter C, Eder K (2006) Conjugated linoleic acids exert similar actions on prostanoid release from aortic and coronary artery smooth muscle cells. Int J Vitam Nutr Res 76:281–289CrossRef

30.

Schleser S, Ringseis R, Eder K (2006) Conjugated linoleic acids have no effect on TNFα-induced adhesion molecule expression, U937 monocyte adhesion, and chemokine release in human aortic endothelial cells. Atherosclerosis 186:337–344CrossRef

31.

Shen J, Halenda SP, Sturek M, Wilden PA (2005) Novel mitogenic effect of adenosine on coronary artery smooth muscle cells: role for the A 1 adenosine receptor. Circ Res 96:982–990CrossRef

32.

Steinhart H, Rickert R, Winkler K (2003) Identification and analysis of conjugated linoleic acid isomers (CLA). Eur J Med Res 8:370–372

33.

Straus DS, Pascual G, Li M, Welch JS, Ricote M, Hsiang CH, Sengchanthalangsy LL, Ghosh G, Glass CK (2000) 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA 97:4844–4849CrossRef

34.

Suganami T, Mori K, Tanaka I, Mukoyama M, Sugawara A, Makino H, Muro S, Yahat K, Ohuchida S, Maruyama T, Narumiya S, Nakao K (2003) Role of prostaglandin E receptor EP1 subtype in the development of renal injury in genetically hypertensive rats. Hypertension 42:1183–1190CrossRef

35.

Toomey S, Roche HM, Fitzgerald D, Belton O (2003) Regression of pre-established atherosclerosis in the apoE^-/- mouse by conjugated linoleic acid. Biochem Soc Trans 31:1075–1079CrossRef

36.

Toomey S, Harhen B, Roche HM, Fitzgerald D, Belton O (2006) Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis 187:40–49CrossRef

37.

Torres-Duarte AP, Vanderhoek JY (2003) Conjugated linoleic acid exhibits stimulatory and inhibitory effects on prostanoid production in human endothelial cells and platelets. Biochim Biophys Acta 1640:169–176

38.

Vistica DT, Skehan P, Scudiero D, Monks A, Pittman A, Boyd MR (1991) Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production. Cancer Res 51:2515–2520

39.

Weldon S, Mitchell S, Kelleher D, Gibney MJ, Roche HM (2004) Conjugated linoleic acid and atherosclerosis: no effect on molecular markers of cholesterol homeostasis in THP-1 macrophages. Atherosclerosis 174:261–273

40.

Yu Y, Correll PH, Vanden Heuvel JP (2002) Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence of PPARγ-dependent mechanism. Biochim Biophys Acta 1581:89–99

41.

Zacharia LC, Jackson EK, Gillespie DG, Dubey RK (2001) Increased 2-methoxyextradiol production in human coronary versus aortic vascular cells. Hypertension 37:658–662

42.

Zheng S, Chen A (2006) Curcumin suppresses the expression of extracellular matrix genes in activated hepatic stellate cells by inhibiting gene expression of connective tissue growth factor. Am J Physiol Gastrointest Liver Physiol 290:G883–G893CrossRef

Title: Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-κB transactivation and collagen formation in human vascular smooth muscle cells
Authors: Dr. Robert Ringseis
Susan Gahler
Klaus Eder
Publication date: 01-03-2008
Publisher: D. Steinkopff-Verlag
Published in: European Journal of Nutrition / Issue 2/2008
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-008-0697-8

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Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-κB transactivation and collagen formation in human vascular smooth muscle cells

Abstract

Background

Aim of the study

Methods

Results

Conclusions

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