التفاصيل البيبلوغرافية
| العنوان: |
Induction of classically activated macrophages results in the loss of anti-contractile effect of perivascular adipose tissue. |
| المؤلفون: |
Murfitt, L. J.1, Withers, S. B.1, Bussey, C. E.1, Heagerty, A. M.1 |
| المصدر: |
Proceedings of the Physiological Society. 2013, p981P-981P. 1/2p. |
| مصطلحات موضوعية: |
*ADIPOSE tissues, *MACROPHAGE activation, *PHARMACOLOGY |
| مستخلص: |
Introduction: Perivascular adipose tissue (PVAT) is now regarded as a metabolically active organ that exerts an anti-contractile effect which is lost in obesity. Here, PVAT undergoes conformational change: there is adipocyte hypertrophy and an increase in the infiltration and activation of macrophages, leading to inflammation. Lean individuals have alternatively activated macrophages (AAMs) but this polarisation shifts to classically activated macrophages (CAMs) with increasing adiposity. These CAMs produce pro-inflammatory cytokines that stimulate inflammation, abrogating the anti-contractile response of PVAT. Previously, we have shown the presence of macrophages in mediating the loss of anti-contractile effect following the induction of experimental hypoxia. (Withers et al. 2011). Therefore, the aim of this study was to determine whether the induction of CAMs by LPS and IFN-γ abrogated the anti-contractile effect of PVAT in vitro. Method: Small segments of mesenteric arteries ±PVAT (diameter 250-300 µm) from male Sprague-Dawley rats (350 g) underwent pharmacological assessment using wire myography. All procedures were performed in accordance with Scientific Procedures Act (1986). Induction of inflammation and CAMs activation was carried out by overnight incubation in Dulbecco's Modified Eagle Medium (DMEM) containing 1 µg/ml LPS and 0.1 µg/ml IFN-γ. Cumulative noradrenaline (1 x 10-9 to 3 x 10-5 M) dose response curves were calculated as a percentage of KCl (60 mM) contraction and expressed as mean±SEM. Data were analysed by two-way ANOVA and Bonferroni post hoc test. P values <0.05 were deemed significant. Results: PVAT exerted an anti-contractile effect compared to no PVAT which is consistent with previous work (PVAT vs. no PVAT: P<0.001, n=7). After induction of inflammation and CAMs activation, PVAT had a significant loss of anti-contractile effect compared to PVAT controls (PVAT control vs. PVAT + LPS/IFN-γ: p=0.0168, n=7). No significant difference was seen in no PVAT vessels treated with LPS and IFN-γ compared to no PVAT controls (no PVAT control vs. no PVAT + LPS/IFN-γ: p=0.7053, n=7). Conclusions: This study indicates a major role of CAMs in the loss of PVAT function as seen in inflammation and obesity. Research is ongoing to ascertain the presence of CAMs and inflammation in LPS and IFN-γ treated ±PVAT mesenteric vessels. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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