title: Cx40 is required for, and cx37 limits, postischemic hindlimb perfusion, survival and recovery.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Physiology, University of Arizona Health Sciences Center, Tucson, Ariz., USA.
authors: Jennifer S
authors: JS
authors: Fang
authors: Stoyan N
authors: SN
authors: Angelov
authors: Alexander M
authors: AM
authors: Simon
authors: Janis M
authors: JM
authors: Burt
mesh_terms: D000818:Animals; D002450:Cell Communication; D017630:Connexins / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein