Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/-mice

Robert S. Crawford, Hassan Albadawi, Alessandro Robaldo, Michael A. Peck, Christopher J. Abularrage, Hyung Jin Yoo, Glenn M. LaMuraglia, Michael T. Watkins

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)952-962
Number of pages11
JournalJournal of Surgical Research
Volume183
Issue number2
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

Apolipoproteins E
Ischemia
Extremities
Chemokine CXCL2
Chemotactic Factors
Keratinocytes
Regeneration
Muscles
Skeletal Muscle
Phenotype
Vascular Endothelial Growth Factor A
Interleukin-6
Angiogenic Proteins
Cytokines
Poly Adenosine Diphosphate Ribose
Skeletal Muscle Fibers
Femoral Artery
Ligation
Lower Extremity
Atherosclerosis

Keywords

  • Cytokines
  • Exercise
  • Growth factors
  • Inflammation
  • Ischemia
  • Reperfusion
  • Skeletal muscle

ASJC Scopus subject areas

  • Surgery

Cite this

Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/-mice. / Crawford, Robert S.; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A.; Abularrage, Christopher J.; Yoo, Hyung Jin; LaMuraglia, Glenn M.; Watkins, Michael T.

In: Journal of Surgical Research, Vol. 183, No. 2, 01.08.2013, p. 952-962.

Research output: Contribution to journalArticle

Crawford, RS, Albadawi, H, Robaldo, A, Peck, MA, Abularrage, CJ, Yoo, HJ, LaMuraglia, GM & Watkins, MT 2013, 'Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/-mice', Journal of Surgical Research, vol. 183, no. 2, pp. 952-962. https://doi.org/10.1016/j.jss.2013.02.042
Crawford, Robert S. ; Albadawi, Hassan ; Robaldo, Alessandro ; Peck, Michael A. ; Abularrage, Christopher J. ; Yoo, Hyung Jin ; LaMuraglia, Glenn M. ; Watkins, Michael T. / Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/-mice. In: Journal of Surgical Research. 2013 ; Vol. 183, No. 2. pp. 952-962.
@article{5bc81b8c7406437795ce1acd3d555a24,
title = "Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/-mice",
abstract = "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.",
keywords = "Cytokines, Exercise, Growth factors, Inflammation, Ischemia, Reperfusion, Skeletal muscle",
author = "Crawford, {Robert S.} and Hassan Albadawi and Alessandro Robaldo and Peck, {Michael A.} and Abularrage, {Christopher J.} and Yoo, {Hyung Jin} and LaMuraglia, {Glenn M.} and Watkins, {Michael T.}",
year = "2013",
month = "8",
day = "1",
doi = "10.1016/j.jss.2013.02.042",
language = "English (US)",
volume = "183",
pages = "952--962",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "2",

}

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

UR - http://www.scopus.com/inward/record.url?scp=84880305697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880305697&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2013.02.042

DO - 10.1016/j.jss.2013.02.042

M3 - Article

VL - 183

SP - 952

EP - 962

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 2

ER -