Resistin Promotes Endothelial Cell Activation
Further Evidence of Adipokine-Endothelial Interaction
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Figure 1. A, Effects of human recombinant resistin (10 to 100 ng/mL, 24 hours) on ET-1 production in cultured endothelial cells. Resistin significantly increased ET-1 release when used at both 50 and 100 ng/mL concentrations. Endothelial cells incubated with resistin (100 ng/mL) plus resistin-neutralizing antibodies (AB) exhibited no increase in ET-1 release. Experiments shown here are representative of 6 independent experiments and were performed in triplicate. *P<0.05, different from resistin 50 and 100 ng/mL. B, Effects of human recombinant resistin (10 to 100 ng/mL) on NO release. Resistin did not affect NO production in endothelial cells at concentrations studied. Experiments shown here are representative of 6 independent experiments and were performed in triplicate. Statistical analysis was performed by ANOVA followed by Fisher protected least squares test.
Figure 2. A, Effects of human recombinant resistin (100 ng/mL, 24 hours) on ET-1 mRNA expression in human endothelial cells. Marked upregulation of ET-1 transcript was noted in resistin-treated cells. Experiments shown here are representative of 6 independent experiments performed in duplicate. *P<0.05, different from control. B, Resistin induces ET-1 promoter activity via AP-1 site. Endothelial cells were transiently transfected with wild-type (wt) or AP-1–mutated ET-1 (mut) promoter luciferase construct, and cells were treated with and without resistin (100 ng/mL). Luciferase activities were measured and normalized against an internal cotransfected β-galactosidase standard. Resistin treatment resulted in induction of ET-1 promoter; however, AP-1–mutated promoter was no longer activated, which suggests that resistin induces ET-1 promoter activity via AP-1 site. Experiments shown are representative of 5 independent experiments performed in duplicate. *P<0.05, different from wild type without resistin and wild type with resistin.
Figure 3. A, Effects of resistin on VCAM-1 expression, determined by flow cytometry. Marked upregulation of VCAM-1 in resistin-treated endothelial cells (50 and 100 ng/mL, 24 hours). Experiments shown are representative of 5 independent experiments performed in duplicate. *P<0.05, different from control. B, Effects of resistin (100 ng/mL) and CD40 ligand (1 μg/mL; CD40-L) on endothelial cell MCP-1 production. Both resistin and CD40-L increase MCP-1 production in endothelial cells. Notably, in resistin-treated cells, CD40-L incites greater increases in MCP-1, which suggests that CD40-L–mediated endothelial cell activation is enhanced by resistin. Experiments shown are representative of 5 independent experiments performed in duplicate. *P<0.05, different from control, and **P<0.05, different from control, resistin, and CD40-L.
Figure 4. Effects of resistin (100 ng/mL, 24 hours) on TRAF-3 expression determined by Western blotting (A). Marked downregulation of TRAF-3 by resistin is observed. TRAF-3 is an inhibitor of CD40 ligand–induced endothelial cell activation. No effects of resistin on CD40 receptor expression were observed (B). Experiments shown are representative of 4 independent experiments performed in triplicate.
Figure 5. Illustrated model of adipokine–endothelial cell interaction. Adipocyte produces numerous hormones and cytokines such as TNF-α, plasminogen activator inhibitor type 1 (PAI-1), leptin, adiponectin, and newly described molecule resistin. These factors play an important role locally (within adipose tissue) but may also have important effects as circulating bioactive factors. Ability of adipokines such as resistin to directly modulate endothelial function and incite endothelial activation may represent an important link between insulin resistance and cardiovascular disease.
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- Resistin Promotes Endothelial Cell ActivationSubodh Verma, Shu-Hong Li, Chao-Hung Wang, Paul W.M. Fedak, Ren-Ke Li, Richard D. Weisel and Donald A.G. MickleCirculation. 2003;108:736-740, originally published August 11, 2003https://doi.org/10.1161/01.CIR.0000084503.91330.49
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