Inhibition of nuclear factor-kappaB attenuates artherosclerosis in apoE/LDLR - double knockout mice.
Nuclear factor - kappaB (NF-kappaB) is a good therapeutic target for cardiovascular disease and numerous efforts are being made to develop safe NF-kappaB inhibitors. Nowadays many authors address NF-kappaB as a major therapeutic target in atherosclerosis, especially for preventive measures, in the light of two main hypothesis of atherosclerosis: oxidation and inflammation. We hypothesized that ammonium pyrrolidinedithioocarbamate (PDTC) - a well-known inhibitor of NF-kappaB could inhibit the development of atherosclerosis in this experimental model. We used apoE/LDLR - DKO mouse model, which is considered as a one of the best models to study the anti-atherosclerotic effect of drugs. In this model PDTC inhibited atherogenesis, measured both by "en face" method (25,15+/-2,9% vs. 15,63+/-0,6%) and "cross-section" method (565867+/-39764 microm2 vs. 291695+/-30384 microm2). Moreover, PDTC did not change the profile of cholesterol and triglycerides in blood. To our knowledge, this is the first report that shows the effect of PDTC on atherogenesis in gene-targeted apoE/LDLR - double knockout mice.
Jawień
J
J
Chair of Pharmacology, Jagiellonian University School of Medicine, Cracow, Poland.
Gajda
M
M
Mateuszuk
Ł
Ł
Olszanecki
R
R
Jakubowski
A
A
Szlachcic
A
A
Korabiowska
M
M
Korbut
R
R
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D013859:Thiocarbamates / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D016328:NF-kappa B; D011759:Pyrrolidines; D011973:Receptors, LDL; D013859:Thiocarbamates; D014280:Triglycerides; C020972:pyrrolidine dithiocarbamic acid; D002784:Cholesterol