Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery

Jennifer S. Fang, Stoyan N. Angelov, Alexander M. Simon, Janis M. Burt

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The unique contributions of connexin (Cx)37 and Cx40, gap junction-forming proteins that are coexpressed in vascular endothelium, to the recovery of tissues from ischemic injury are unknown. We recently reported that Cx37-deficient (Cx37 -/-) animals recovered ischemic hindlimb function more quickly and to a greater extent than wild-type (WT) or Cx40 -/- animals, suggesting that Cx37 limits recovery in the WT animal. Here, we tested the hypothesis that enhanced angio-genesis, arteriogenesis, and vasculogenesis contribute to improved postischemic hindlimb recovery in Cx37 -/- animals. Ischemia was induced unilaterally in the hindlimbs of WT or Cx37 -/- mice (iso-flurane anesthesia). Postsurgical limb appearance, use, and perfusion were documented during recovery, and the number (and size) of large and small vessels was determined. Native collateral number, predominantly established during embryonic development (vasculogenesis), was also determined in the pial circulation. Both microvascular density in the gastrocnemius of the ischemic limb (an angiogenic field) and the number and tortuosity of larger vessels in the gracilis vasculature (an arteriogenic field) were increased in Cx37 -/- animals compared with WT animals. Cx37 -/- mice also had an increased (vs. WT) number of collateral vessels in the pial circulation. These findings suggest that in Cx37 -/- animals, improved recovery of the ischemic hindlimb involves enhanced vasculogenesis, resulting in increased numbers of collaterals in the hindlimb (and pial circulations) and more extensive collateral remodeling and angiogenesis. These results are consistent with Cx37 exerting a growth-suppressive effect in the vasculature that limits embryonic vasculogenesis as well as arteriogenic and angiogenic responses to ischemic injury in the adult animal.

Original languageEnglish (US)
Pages (from-to)H1872-H1881
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 1 2011

Keywords

  • Angiogenesis
  • Arteriogenesis
  • Collateralization
  • Connexin
  • Gap junction
  • Ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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