Analysis Tools
muscle
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• at 14 days after hindlimb ischemia (HLI) induced by unilateral femoral artery ligation, BrdU+ Pax7+ cells are significantly more abundant in the ischemic limb (IL) relative to those in wild-type controls, indicating increased muscle satellite cell proliferation
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• at 14 days after HLI, the average size of muscle fibers in the gastrocnemius muscle is significantly reduced in both the IL and NIL, whereas no changes are seen in wild-type controls; however, no difference in muscle morphology is noted by 28 days after HLI
• at 14 days after HLI, the area of necrosis in the ischemic gastrocnemius muscle is significantly reduced relative to that in wild-type controls
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• after hindlimb ischemia (HLI), mice show enhanced skeletal muscle repair in both the ischemic limb (IL) and contralateral non-ischemic limb (NIL)
• at 14-28 days after HLI, blood flow and the number of capillaries per muscle fiber is significantly increased in both the IL and NIL
• at 14 days (but not at 28 days) after HLI, the average size of muscle fibers in the gastrocnemius muscle is significantly reduced in both the IL and NIL, unlike in wild-type controls
• at 14 days after HLI, ischemic gastrocnemius muscles show markedly less necrosis and a significant increase in myogenin levels along with a decrease in myosin heavy chain (MHC) levels, while at 28 days MHC levels are higher but myogenin levels are similar to those in wild-type controls
• at 14 but not 28 days after HLI, mice exhibit transiently elevated levels of TNFSF12 (TWEAK)-mediated activation of NF-kappaB and Notch signaling in both the IL and NIL which lead to enhanced myogenesis/angiogenesis not limited to the site of injury
• by 28 days after HLI, increased NF-kappaB and Notch activation is resolved leading to enhanced muscle regeneration
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cellular
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• at 3-5 days after HLI, mice exhibit increased macrophage accumulation in the IL, as shown by Mac-3 staining
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• at 14 days after hindlimb ischemia (HLI) induced by unilateral femoral artery ligation, BrdU+ Pax7+ cells are significantly more abundant in the ischemic limb (IL) relative to those in wild-type controls, indicating increased muscle satellite cell proliferation
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• at 14 days after HLI, State3 mitochondria isolated from IL and NIL show a significant decrease in substrate oxidation, indicating suppression of mitochondrial respiration
• respiratory control ratio (State3/State4 respiration) is significantly decreased in both the IL and NIL
• glycolytic transcripts are significantly increased in both the IL and NIL
• however, no differences in mitochondrial respiration or glycolytic transcripts are observed in unligated mice
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homeostasis/metabolism
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• at 14 but not 28 days after HLI, plasma TNFSF12 levels (aka TWEAK, a secreted pro-inflammatory cytokine of the tumor necrosis factor family) are significantly elevated relative to those in wild-type controls
• transiently elevated levels of TNFSF12 stimulate muscle satellite cell proliferation and tissue regeneration in both the IL and NIL after ischemic muscle injury
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• at 25-38 days after HLI, total running wheel distance is significantly increased relative to that in wild-type controls, indicating enhanced functional recovery
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immune system
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• at 3-5 days after HLI, mice exhibit increased macrophage accumulation in the IL, as shown by Mac-3 staining
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• at 14 but not 28 days after HLI, plasma TNFSF12 levels (aka TWEAK, a secreted pro-inflammatory cytokine of the tumor necrosis factor family) are significantly elevated relative to those in wild-type controls
• transiently elevated levels of TNFSF12 stimulate muscle satellite cell proliferation and tissue regeneration in both the IL and NIL after ischemic muscle injury
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hematopoietic system
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• at 3-5 days after HLI, mice exhibit increased macrophage accumulation in the IL, as shown by Mac-3 staining
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cardiovascular system
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• at P6, retinas show increased vessel growth and stalk/connector cell formation, but decreased tip cell branching and filopodia, suggesting Notch activation during retinal vascular patterning
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vision/eye
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• at P6, retinas show increased vessel growth and stalk/connector cell formation, but decreased tip cell branching and filopodia, suggesting Notch activation during retinal vascular patterning
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limbs/digits/tail
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• at 14 days after HLI, the average size of muscle fibers in the gastrocnemius muscle is significantly reduced in both the IL and NIL, whereas no changes are seen in wild-type controls; however, no difference in muscle morphology is noted by 28 days after HLI
• at 14 days after HLI, the area of necrosis in the ischemic gastrocnemius muscle is significantly reduced relative to that in wild-type controls
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