Cx40 is required for, and Cx37 limits, postischemic hindlimb perfusion, survival and recovery

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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background/Aims: Ischemia induced by large-vessel obstruction or vascular injury induces a complex cascade of vasodilatory, remodeling and inflammatory pathways; coordination of these processes by vascular endothelium is likely to involve endothelial gap junctions. Vascular endothelium predominantly expresses two connexin (Cx) isoforms: Cx37 and Cx40. The relevance of these Cxs to postischemic limb recovery remains unclear. Methods: In this study, we use a well-established, severe femoral-saphenous artery-vein pair resection model of unilateral hindlimb ischemia to test the relevance of Cx37 and Cx40 to postischemic tissue survival and recovery of limb perfusion. Results: Cx40-deficient animals (Cx40-/-) experienced a severe reduction in limb perfusion relative to wild-type (WT) animals and exhibited profound and rapid failure of ischemic limb survival. By contrast, the deficit in limb perfusion was less severe in Cx37-ablated (Cx37-/-) animals compared to WT, corresponding with more rapid recovery of limb appearance and use. These results demonstrate that Cx40 is necessary for postischemic limb survival and reperfusion, whereas Cx37 deletion reduces the extent of ischemia in the same model. Conclusion: In summary, we present evidence demonstrating that Cx37 and Cx40 uniquely regulate postischemic limb perfusion, altering the severity of ischemic insult and consequent postischemic survival.

Original languageEnglish (US)
Pages (from-to)2-12
Number of pages11
JournalJournal of Vascular Research
Volume49
Issue number1
DOIs
StatePublished - Dec 2011

Fingerprint

Hindlimb
Extremities
Perfusion
Ischemia
Vascular Endothelium
Tissue Survival
Connexins
Wild Animals
Gap Junctions
Vascular System Injuries
Saphenous Vein
Femoral Artery
Reperfusion
Protein Isoforms

Keywords

  • Cx37
  • Cx40
  • Gap junction
  • Ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cx40 is required for, and Cx37 limits, postischemic hindlimb perfusion, survival and recovery. / Fang, Jennifer S.; Angelov, Stoyan N.; Simon, Alex; Burt, Janis M.

In: Journal of Vascular Research, Vol. 49, No. 1, 12.2011, p. 2-12.

Research output: Contribution to journalArticle

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