Moderate levels of ethanol induce expression of vascular endothelial growth factor and stimulate angiogenesis.
Alcohol abuse has a negative impact on human health; however, epidemiological studies show that moderate consumption of ethanol (EtOH) reduces the risk of coronary heart disease, sudden cardiac death, and ischemic stroke. The mechanisms for these reductions in cardiovascular disease are not well established. Using cultured coronary artery vascular smooth muscle cells, we found that moderate levels of EtOH (10 and 20 mM) caused dose-related increases in both vascular endothelial growth factor (VEGF) mRNA (Northern blot) expression (1.9- and 2.6-fold) and VEGF protein (ELISA) expression (19 and 68%) compared with control (P < 0.05). EtOH at 0.25 g. kg(-1). day(-1) (7 days) increased VEGF mRNA expression by 1.48-fold over control, and increased vessel length density from 3.9 +/- 0.7 (control) to 6.0 +/- 0.3 mm/mm(2) (P < 0.05) in chick chorioallantoic membrane (CAM). We conclude that moderate levels of ethanol can induce VEGF expression and stimulate angiogenesis in chick CAM. Therefore, the results provide a theoretical basis for speculating that the cardiovascular-protective effects of moderate alcohol consumption may be partly mediated through VEGF-induced angiogenesis.
Gu
J W
JW
Angiogenesis Research Laboratories, Department of Physiology, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. jgu@physiology.umsmed.edu
Elam
J
J
Sartin
A
A
Li
W
W
Roach
R
R
Adair
T H
TH
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000502:physiology; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002492:Central Nervous System Depressants; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000431:Ethanol