ArticleVascular medicine (London, England)2009
Dual roles of tumor necrosis factor-alpha receptor-1 in a mouse model of hindlimb ischemia.
Article in Vascular medicine (London, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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0 citing papers in PubMed, 2 citations in OpenAlex.
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5 authors at 3 institutions in 2 countries.
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Abstract
Signals in the tumor necrosis factor alpha (TNF-alpha) pathway are upregulated after ischemia, yet its role in peripheral ischemia remains unclear. We investigated the effect of TNF-alpha receptor 1 (TNFR-1) in acute limb ischemia of TNFR-1 knockout (TNFR-1-/-) and wild type (WT, TNFR-1+/+) mice. Laser Doppler scanning showed that although pre-ischemia blood flow levels were similar in these mice, the limb reperfusion after ischemia was significantly higher in TNFR-1-/- mice 1-7 days after injury. Consistently, fewer TUNEL-positive cells, less DNA fragmentation, and a lower ischemic score were detected in the TNFR-1-/- group when compared to WT controls. Western blot analysis revealed less expression of pro-apoptotic markers Bax and cleaved caspase-3 in TNFR-1-/- mice 1 day after ischemia, supporting the hypothesis that the absence of TNFR-1 results in a reduction of apoptosis. The rate of post-ischemia amputation was 50% in WT mice versus 0% in TNFR-1-/- mice. However, immunohistochemical co-staining of microvessel marker CD31 and cellular proliferation marker BrdU 21 days after ischemia showed an impaired angiogenic activity in the TNFR-1-/- mice. These data were supported by Western blot analysis, which indicated a decreased expression of angiopoietin-1 (Ang-1) and its receptor Tie-2 in TNFR-1-/- mice. Our results suggest that a deficiency in TNFR-1 prevents the activation of death-related proteins downstream to TNF-alpha and attenuates apoptosis in acute limb ischemia, but the lack of TNFR-1 signaling hinders the belated angiogenesis mediated by the Ang-1/Tie-2 pathway.
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