Abstract 148: Stat2 Deficiency Does Not Protect From Atherosclerosis in Ldlr Knockout Mice Fed a Western Diet
Signal Transducer and Activator of Transcription (Stat2) is a transcription factor that plays a critical role in type I interferon (IFN) signaling. Recent evidence supports a role for the type I IFN pathway in atherosclerosis, since recombinant IFN alpha and IFN beta both promote atherosclerosis in mice. We tested the hypothesis that constitutive type I IFN signaling through STAT2 may promote atherosclerotic lesion formation. Male Ldlr KO and Stat2/Ldlr DKO mice on a C57BL6/J background were fed a western diet for 16 weeks. Total cholesterol levels were indistinguishable at baseline (Ldlr KO: 232 ± 24 vs. Stat2/Ldlr DKO: 239 ± 36 mg/dl, p=0.39), but significantly higher in the Stat2/Ldlr DKO mice after 16 weeks of western diet (Ldlr KO: 856 ± 203 Vs Stat2/Ldlr DKO: 1015 ± 176 mg/dl, p=0.004). Despite consuming less food than Ldlr KO controls, the Stat2/Ldlr DKO animals weighed significantly more than controls and had greater fat mass in the inguinal subcutaneous and perigonadal depots respectively (Ldlr KO: 0.45±0.23 Vs Stat2/Ldlr DKO: 0.69 ± 0.27 g, p=0.003 and Ldlr KO: 0.89 ± 0.50 Vs Stat2/Ldlr DKO: 1.39 ± 0.56 g, p=0.003). Surprisingly, no significant differences were observed in percent lesional area of aortae (Ldlr KO: 9.7% ± 5.6% Vs Stat2/Ldlr DKO: 12.5% ± 6.8%, p=0.156). In conclusion, STAT2 does not appear to have a major impact on atherosclerosis in the absence of exogenous type I IFNs or other agonism of the pathway.
Author Disclosures: R. Gupta: None. C. Schindler: None. H. Wu: None. C. Ballantyne: None. W.R. Lagor: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.