Density, calibre and ramification of muscle capillaries are altered in a mouse model of severe spinal muscular atrophy

E Somers, Z Stencel, T M Wishart, T H Gillingwater, S H Parson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA) is traditionally described and characterised as a disease of the neuromuscular system. Recently, the vascular system has been implicated in SMA pathogenesis, but there are no reports on whether this impacts on skeletal muscle microvasculature. Using an established mouse model of severe SMA (Smn(-/-);SMN2(+/+)), we examined the capillary bed in three different skeletal muscles using quantitative imaging and western blotting in late symptomatic mice (P5). We found a dramatic (45%) decrease in the density of the capillary bed in all muscles examined compared to littermate controls at early and late symptomatic time points, and reduced expression of a key endothelial protein, PECAM-1. In addition, capillary calibre was increased by 50% in SMA mice while ramification of capillaries into muscle was reduced. Investigation of earlier developmental time points revealed identical changes at an early symptomatic time point (P3), but significantly, no difference at a pre-symptomatic time point (P1). These changes are likely to have considerable impact on the ability of the muscle capillary bed to deliver oxygen and remove metabolites from muscle and may therefore contribute to pathogenesis in SMA.

Original languageEnglish
Pages (from-to)435-442
Number of pages8
JournalNeuromuscular Disorders
Volume22
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • animals
  • animals, newborn
  • antigens, CD31
  • disease models, animal
  • mice
  • mice, knockout
  • motor neurons
  • muscular atrophy, spinal
  • survival of motor neuron 1 protein

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