Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound healing

Abstract

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.

Effects of a Single Dose of Ethanol on Survival Rate and Angiogenesis of Chick Embryo

“…However, higher dose at 10% EtOH inhibit angiogenesis. Inhibition of angiogenesis has also been reported in studies carried out on chick embryo and on wound healing (Radek, Matthies et al 2005;Radek, Kovacs et al 2008). This suggests that EtOH inhibit the angiogenesis at higher doses.…”

Acute ethanol exposure disrupts VEGF receptor cell signaling in endothelial cells

“…After 8 h, the ethanol media was replaced with fresh ethanol-free media, and the cells incubated for another 8 h. The cells were then trypsinized and incubated on an elliptical rotator at a concentration of 5 ϫ 10 5 for 30 min at room temperature with media in the presence or absence of 100 ng/ml of murine VEGF 164 (mVEGF164) (R&D Systems, Minneapolis, MN). Following incubation, cord formation was assessed as described previously (30,40). For each independent experiment, the number of endothelial cordlike structures formed in the presence of control mVEGF 164 was considered maximal (100%), and experimental values were determined as a percentage of maximal cord formation.…”

“…Recent studies in our laboratory demonstrated that mice with a blood alcohol concentration (BAC) of 0.1% (100 mg/dl) at the time of injury exhibited a 50% reduction in wound vascularity (40). The reduction in vascularity occurred even though the level of VEGF in the wounds from ethanol-exposed mice was greater than that of control.…”

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

“…Relevant murine models demonstrate that acute alcohol consumption decreases the expression of VEGF receptors and reduces nuclear expression of HIF-1α in endothelial cells, thereby affecting angiogenesis and the proliferative phase of wound healing [69,70]. There are also studies showing that inappropriate alcohol consumption has an adverse effect on the physiologic reepithelialisation and collagen production [69][70][71][72].…”