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Updated: Aug 15, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Inhibition of nuclear factor-kappaB attenuates artherosclerosis in apoE/LDLR - double knockout mice
J Jawień1, M Gajda, Ł Mateuszuk
1Chair of Pharmacology, Jagiellonian University School of Medicine, Cracow, Poland.
Abstract:
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.
Insights
Ammonium pyrrolidinedithiocarbamate (PDTC), an inhibitor of Nuclear factor-kappaB (NF-kappaB), effectively reduced atherosclerosis development in a mouse model. This study demonstrates PDTC
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Nuclear factor-kappaB (NF-kappaB) is implicated in cardiovascular disease pathogenesis.
- NF-kappaB inhibition is a key therapeutic strategy for atherosclerosis.
- Atherosclerosis is driven by inflammatory and oxidative processes.
Purpose of the Study:
- To investigate the anti-atherosclerotic effects of ammonium pyrrolidinedithiocarbamate (PDTC).
- To evaluate PDTC's efficacy in a relevant preclinical model of atherosclerosis.
Main Methods:
- Utilized the apoE/LDLR-double knockout (DKO) mouse model.
- Administered PDTC, a known NF-kappaB inhibitor.
- Quantified atherosclerotic lesion development using "en face" and "cross-section" methods.
Main Results:
- PDTC significantly inhibited atherogenesis in apoE/LDLR-DKO mice.
- Lesion reduction was observed via both "en face" (25.15% vs. 15.63%) and "cross-section" (565,867 µm² vs. 291,695 µm²) analyses.
- PDTC did not alter blood cholesterol or triglyceride profiles.
Conclusions:
- PDTC demonstrates significant anti-atherosclerotic properties in a genetic mouse model.
- This study provides the first evidence of PDTC's efficacy against atherogenesis in apoE/LDLR-DKO mice.
- NF-kappaB inhibition via PDTC represents a potential therapeutic avenue for atherosclerosis.
