title: Ethanol protects from injury due to ischemia and reperfusion by increasing vascularity via vascular endothelial growth factor.
abstract: The cardioprotective effects of moderate ethanol consumption have been known for years and have generally been ascribed to long-term effects of alcohol on blood lipids. However, other mechanisms, particularly ethanol-induced increase in blood vessel density, may also be involved. Our goal was to understand the relationship between ethanol consumption, new blood vessel formation in vivo and protection from injury due to ischemia and ischemia/reperfusion. Using paired ethanol fed and control rats, we assessed capillary density in the heart, brain and skeletal muscle by immunostaining and quantified expression of vascular endothelial growth factor (VEGF) by Western blot analysis and immunocytochemistry. Numbers of vessels were significantly increased in the brain, heart and skeletal muscle of animals fed ethanol-rich diets. VEGF (and its receptors) were upregulated in these organs. These effects were very rapid: highly significantly increased vascularization was seen within 2 weeks of commencing alcohol feeding. A neutralizing VEGF antibody, bevacizumab, inhibited new blood vessel formation induced by moderate doses of ethanol. Ethanol consumption increased vascularization and promoted skeletal muscle regeneration following hindlimb ischemia; these effects were prevented by bevacizumab. Finally, ethanol consumption protected myocardium following experimental ischemia/reperfusion.
  
  
  CONCLUSIONS
  Experimental ethanol ingestion rapidly increases VEGF production, significantly increasing the capillary bed in the heart, brain, and skeletal muscle. Moreover, the ethanol-induced increase of blood vessel density is protective against ischemic events (i.e., hindlimb ischemia and myocardium ischemia/reperfusion) and promotes skeletal muscle regeneration.
authors.affiliation: Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jplouboutin@hotmail.com
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Louboutin
authors.forename: Elena
authors.initials: E
authors.lastname: Marusich
authors.forename: Ehre
authors.initials: E
authors.lastname: Gao
authors.forename: Lokesh
authors.initials: L
authors.lastname: Agrawal
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: David S
authors.initials: DS
authors.lastname: Strayer
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000068258:Bevacizumab; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000254:growth & development; D003331:Coronary Vessels / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000431:Ethanol