TY - JOUR
T1 - Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/-mice
AU - Crawford, Robert S.
AU - Albadawi, Hassan
AU - Robaldo, Alessandro
AU - Peck, Michael A.
AU - Abularrage, Christopher J.
AU - Yoo, Hyung Jin
AU - LaMuraglia, Glenn M.
AU - Watkins, Michael T.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - Background: We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Methods: Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Results: Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Conclusions: Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration.
AB - Background: We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Methods: Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Results: Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Conclusions: Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration.
KW - Cytokines
KW - Exercise
KW - Growth factors
KW - Inflammation
KW - Ischemia
KW - Reperfusion
KW - Skeletal muscle
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U2 - 10.1016/j.jss.2013.02.042
DO - 10.1016/j.jss.2013.02.042
M3 - Article
C2 - 23528286
AN - SCOPUS:84880305697
VL - 183
SP - 952
EP - 962
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 2
ER -