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Reduced endothelial dependent vasodilation in vessels from TLR4(-/-) mice is associated with increased superoxide generation.

Harrington LS, Lundberg MH, Waight M, Rozario A, Mitchell JA - Biochem. Biophys. Res. Commun. (2011)

Bottom Line: Using the isometric wire myograph, mesenteric artery vasodilator responses to acetylcholine and MnCl(2) (a superoxide dismutase mimetic) were measured.Our observations suggest that loss of TLR4 increases superoxide generation which reduces the biological activity of endothelial derived nitric oxide and thereby explains the endothelial dysfunction and associated cardiovascular phenotype in TLR4(-/-) mice.These data implicate a novel cardio-protective role for TLR4 in vascular homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Cardiothoracic Pharmacology, NHLI, Imperial College, Dovehouse Street, London, UK. l.harrington@imperial.ac.uk

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Superoxide levels in the smooth muscle cell layer of (A) wild type and TLR4−/− arteries, with or without MnCl2. Left hand side images show arteries incubated with DHE which produces 2-hydroxyethidium when oxidised by ; middle images show blue fluorescence of the nuclear stain DAPI; right hand side images show DHE and DAPI combined. (B) Data are represented as mean pixel count ± SEM. ∗p < 0.05 compared to wild type; #p < 0.05 for plus MnCl2 versus TLR4−/− control by one-way ANOVA followed by Bonferroni’s Multiple Comparison Test, n = 6 mice. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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f0020: Superoxide levels in the smooth muscle cell layer of (A) wild type and TLR4−/− arteries, with or without MnCl2. Left hand side images show arteries incubated with DHE which produces 2-hydroxyethidium when oxidised by ; middle images show blue fluorescence of the nuclear stain DAPI; right hand side images show DHE and DAPI combined. (B) Data are represented as mean pixel count ± SEM. ∗p < 0.05 compared to wild type; #p < 0.05 for plus MnCl2 versus TLR4−/− control by one-way ANOVA followed by Bonferroni’s Multiple Comparison Test, n = 6 mice. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Mentions: In parallel experiments superoxide levels in the endothelial cell (Fig. 3) and smooth muscle cell (Fig. 4) layers of mesenteric arteries were visualised and quantified in vessels from wild type and TLR4−/− mice. In vessels from wild type mice, superoxide levels were relatively low and not significantly inhibited by MnCl2. By contrast levels of superoxide were greatly increased in both endothelial cell and smooth muscle cell layers in arteries from TLR4−/− mice and reduced to control levels in the presence of MnCl2 (Figs. 3 and 4).


Reduced endothelial dependent vasodilation in vessels from TLR4(-/-) mice is associated with increased superoxide generation.

Harrington LS, Lundberg MH, Waight M, Rozario A, Mitchell JA - Biochem. Biophys. Res. Commun. (2011)

Superoxide levels in the smooth muscle cell layer of (A) wild type and TLR4−/− arteries, with or without MnCl2. Left hand side images show arteries incubated with DHE which produces 2-hydroxyethidium when oxidised by ; middle images show blue fluorescence of the nuclear stain DAPI; right hand side images show DHE and DAPI combined. (B) Data are represented as mean pixel count ± SEM. ∗p < 0.05 compared to wild type; #p < 0.05 for plus MnCl2 versus TLR4−/− control by one-way ANOVA followed by Bonferroni’s Multiple Comparison Test, n = 6 mice. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105224&req=5

f0020: Superoxide levels in the smooth muscle cell layer of (A) wild type and TLR4−/− arteries, with or without MnCl2. Left hand side images show arteries incubated with DHE which produces 2-hydroxyethidium when oxidised by ; middle images show blue fluorescence of the nuclear stain DAPI; right hand side images show DHE and DAPI combined. (B) Data are represented as mean pixel count ± SEM. ∗p < 0.05 compared to wild type; #p < 0.05 for plus MnCl2 versus TLR4−/− control by one-way ANOVA followed by Bonferroni’s Multiple Comparison Test, n = 6 mice. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Mentions: In parallel experiments superoxide levels in the endothelial cell (Fig. 3) and smooth muscle cell (Fig. 4) layers of mesenteric arteries were visualised and quantified in vessels from wild type and TLR4−/− mice. In vessels from wild type mice, superoxide levels were relatively low and not significantly inhibited by MnCl2. By contrast levels of superoxide were greatly increased in both endothelial cell and smooth muscle cell layers in arteries from TLR4−/− mice and reduced to control levels in the presence of MnCl2 (Figs. 3 and 4).

Bottom Line: Using the isometric wire myograph, mesenteric artery vasodilator responses to acetylcholine and MnCl(2) (a superoxide dismutase mimetic) were measured.Our observations suggest that loss of TLR4 increases superoxide generation which reduces the biological activity of endothelial derived nitric oxide and thereby explains the endothelial dysfunction and associated cardiovascular phenotype in TLR4(-/-) mice.These data implicate a novel cardio-protective role for TLR4 in vascular homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Cardiothoracic Pharmacology, NHLI, Imperial College, Dovehouse Street, London, UK. l.harrington@imperial.ac.uk

Show MeSH
Related in: MedlinePlus