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Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice.

Publication ,  Journal Article
McClung, JM; McCord, TJ; Keum, S; Johnson, S; Annex, BH; Marchuk, DA; Kontos, CD
Published in: Am J Pathol
May 2012

Genetics plays an important role in determining peripheral arterial disease (PAD) pathology, which causes a spectrum of clinical disorders that range from clinically silent reductions in blood flow to limb-threatening ischemia. The cell-type specificity of PAD pathology, however, has received little attention. To determine whether strain-dependent differences in skeletal muscle cells might account for the differential responses to ischemia observed in C57BL/6 and BALB/c mice, endothelial and skeletal muscle cells were subjected to hypoxia and nutrient deprivation (HND) in vitro, to mimic ischemia. Muscle cells were more susceptible to HND than were endothelial cells. In vivo, C57BL/6 and BALB/c mice displayed strain-specific differences in myofiber responses after hindlimb ischemia, with significantly greater myofiber atrophy, greater apoptosis, and attenuated myogenic regulatory gene expression and stress-responsive signaling in BALB/c mice. Strain-specific deficits were recapitulated in vitro in primary muscle cells from both strains after HND. Muscle cells from BALB/c mice congenic for the C57BL/6 Lsq-1 quantitative trait locus were protected from HND-induced atrophy, and gene expression of vascular growth factors and their receptors was significantly greater in C57BL/6 primary muscle cells. Our results indicate that the previously identified specific genetic locus regulating strain-dependent collateral vessel density has a nonvascular or muscle cell-autonomous role involving both the myogenic program and traditional vascular growth factor receptor expression.

Duke Scholars

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

May 2012

Volume

180

Issue

5

Start / End Page

2156 / 2169

Location

United States

Related Subject Headings

  • Species Specificity
  • Signal Transduction
  • Receptors, Growth Factor
  • Pathology
  • Muscular Atrophy
  • Muscle, Skeletal
  • Muscle Fibers, Skeletal
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
 

Citation

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MLA
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McClung, J. M., McCord, T. J., Keum, S., Johnson, S., Annex, B. H., Marchuk, D. A., & Kontos, C. D. (2012). Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice. Am J Pathol, 180(5), 2156–2169. https://doi.org/10.1016/j.ajpath.2012.01.032
McClung, Joseph M., Timothy J. McCord, Sehoon Keum, Soraya Johnson, Brian H. Annex, Douglas A. Marchuk, and Christopher D. Kontos. “Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice.Am J Pathol 180, no. 5 (May 2012): 2156–69. https://doi.org/10.1016/j.ajpath.2012.01.032.
McClung JM, McCord TJ, Keum S, Johnson S, Annex BH, Marchuk DA, et al. Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice. Am J Pathol. 2012 May;180(5):2156–69.
McClung, Joseph M., et al. “Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice.Am J Pathol, vol. 180, no. 5, May 2012, pp. 2156–69. Pubmed, doi:10.1016/j.ajpath.2012.01.032.
McClung JM, McCord TJ, Keum S, Johnson S, Annex BH, Marchuk DA, Kontos CD. Skeletal muscle-specific genetic determinants contribute to the differential strain-dependent effects of hindlimb ischemia in mice. Am J Pathol. 2012 May;180(5):2156–2169.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

May 2012

Volume

180

Issue

5

Start / End Page

2156 / 2169

Location

United States

Related Subject Headings

  • Species Specificity
  • Signal Transduction
  • Receptors, Growth Factor
  • Pathology
  • Muscular Atrophy
  • Muscle, Skeletal
  • Muscle Fibers, Skeletal
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice