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


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


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


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


CONCLUSIONS
CLA isomers inhibit PDGF-stimulated collagen production by vascular SMCs, which is considered to be a hallmark of atherosclerosis, in a PPARgamma-dependent manner. Whether inhibition of the NF-kappaB-pathway is of significance for the reduction of collagen formation by CLA isomers needs further investigation.
Ringseis
Robert
R
Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität, Halle-Wittenberg, Emil-Abderhalden-Strasse 26, 06108, Halle/Saale, Germany. robert.ringseis@landw.uni-halle.de
Gahler
Susan
S
Eder
Klaus
K
D000704:Analysis of Variance; D050197:Atherosclerosis / Q000378:metabolism*; D001549:Benzamides; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D019787:Linoleic Acid / Q000737:chemistry / Q000494:pharmacology; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011725:Pyridines
D001549:Benzamides; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; D047495:PPAR gamma; D010982:Platelet-Derived Growth Factor; D011725:Pyridines; C458508:T 0070907; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; D003094:Collagen; D019787:Linoleic Acid