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Signal transducer and activator of transcription‐1 deficient mice are protected from hypercholesterolemic diet‐induced endothelial dysfunction.
Author(s) -
Huang Hong,
Han Bing,
Bauer John A.,
Hoyt Dale G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a730
Subject(s) - endocrinology , medicine , stat1 , endothelial dysfunction , acetylcholine , stat protein , chemistry , ovariectomized rat , phenylephrine , endothelium , activator (genetics) , stat3 , phosphorylation , receptor , biochemistry , estrogen , blood pressure
Endothelial dysfunction is an initiating event in atherogenesis that may be related to pro‐inflammatory effects of hypercholesterolemia‐inducing diets (HCD). Signal transducer and activator of transcription‐1 (STAT1) mediates many responses to inflammatory cytokines. Thus we measured the effects of feeding HCD or control diet (CD) for 16 weeks on STAT1 wildtype (WT) and knockout (KO) mice. Endothelial function was measured by acetylcholine‐dependent vasodilatation in vitro using isolated aortas pre‐contracted with phenylephrine. STAT1 activation was assessed by western blotting for phosphorylated tyrosine 701 and serine 727. HCD increased plasma cholesterol and LDL in both strains of mice by similar amounts. HCD activated STAT1 in WT mice in various tissues (liver, spleen, and lung were tested). The maximum relaxation of aortas due to acetylcholine in WT mice fed CD was 84.0 ± 7.0% (i.e. tension was reduced to ~16% of the pre‐contracted level), but only 3.3 ± 5.3% after HCD. STAT1 KO mice were partially resistant to HCD as relaxation was 29.9 ± 6.4% (p=0.005 vs. WT on HCD). The results suggest that STAT1 plays an important role in HCD‐induced endothelial dysfunction. (Support: Ohio Valley AHA 0525318B).