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Am J Physiol Heart Circ Physiol 289: H1084-H1090, 2005. First published April 29, 2005; doi:10.1152/ajpheart.00080.2005
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Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound healing

Katherine A. Radek,1,2,3 Annette M. Matthies,1,4 Aime L. Burns,1 Scott A. Heinrich,1,2,5 Elizabeth J. Kovacs,1,2,5 and Luisa A. DiPietro1,2,6

1Burn and Shock Trauma Institute, 2Alcohol Research Program, 3Division of Molecular and Cellular Biochemistry, 4Departments of Microbiology and Immunology; 5Cell Biology, Neurobiology, and Anatomy; and 6Surgery, Loyola University Medical Center, Maywood, Illinois

Submitted 27 January 2005 ; accepted in final form 22 April 2005

Acute ethanol exposure represents an increased risk factor for morbidity and mortality associated with surgical or traumatic injury. Despite clinical observations suggesting that ethanol exposure before injury alters tissue repair processes, little direct evidence about the mechanism by which ethanol affects the wound healing process is available. In this study, excisional wounds from female BALB/c mice with or without circulating ethanol levels of 100 mg/dl were used to assess wound closure, angiogenesis, and collagen content. Ethanol exposure resulted in a significant but transient delay in wound closure at day 2 postwounding (28 ± 4% vs. 17 ± 1%). In addition, total collagen content was significantly reduced by up to 37% in wounds from ethanol-treated mice compared with controls. The most significant effect of ethanol exposure on wounds was on vascularity because angiogenesis was reduced by up to 61% in wounds from ethanol-treated mice. The reduction in vessel density occurred despite near-normal levels of proangiogenic factors VEGF and FGF-2, suggesting a direct effect of ethanol exposure on endothelial cell function. Further evidence for a direct effect was observed in an in vitro angiogenesis assay because the exposure of endothelial cells to ethanol reduced angiogenic responsiveness to just 8.33% of control in a cord-forming assay. These studies provide novel information regarding the effect of a single dose of ethanol on multiple parameters of the wound healing process in vivo and suggest a potential mechanism by which ethanol impairs healing after traumatic injury.

tissue repair; angiogenesis; murine; skin



Address for reprint requests and other correspondence: L. A. DiPietro, Burn and Shock Trauma Institute, Loyola University Medical Center, 2160 S. First Ave., Maywood, IL 60153 (e-mail: ldipiet{at}lumc.edu)




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