Alcohol reduces MMP-2 in humans and isolated smooth muscle cells.
Alcoholic beverages are known to exert a protective effect on atherosclerotic disease. This study aimed to assess the in vivo and in vitro effects of alcohol on matrix metalloproteinase (MMP) -2 and -9, known to determine atherosclerosis progression. Eighteen healthy volunteers, regular drinkers (two standard alcohol servings/day, on average) at first examination (baseline) were asked to abstain from any alcoholic beverage for one week (abstention), and then to assume two standard alcohol servings of beer daily for 1 week (re-exposure). Activity of MMP-2 and -9, total antioxidant activity (AOA), glutathione (GSH) plasma levels were carried out at baseline, at the end of abstention, and after 1 week of re-exposure. To validate the in vivo results, MMP-2 activity and expression, AOA, and GSH, were determined in human smooth muscle cells treated for 96 h with increasing concentrations (12.5-100 mM) of ethanol. MMP-2, but not MMP-9 plasma activity was higher at abstention than at baseline or re-exposure (P<.001 and P< or =.005, respectively). Changes in AOA and GSH throughout the study were not significant. No correlation was found between MMPs and antioxidant activity. In vitro, ethanol at 25 mM reduced by around 10% MMP-2 activity (P=.003) in smooth muscle cells, whereas MMP-2 expression, AOA, and GSH were unaffected. Alcohol reduces MMP-2 plasma activity in healthy humans and in isolated vascular smooth muscle cells. This in vitro reduction is unrelated to MMP-2 expression in vascular cells or to antioxidant levels changes.
Fiotti
Nicola
N
S.C. Clinica Medica Generale e Terapia Medica, Department of Scienze Cliniche, Morfologiche e Tecnologiche, University of Trieste, Strada di Fiume, 447, 34149 Trieste, Italy. fiotti@units.it
Tubaro
Franco
F
Altamura
Nicola
N
Grassi
Gabriele
G
Moretti
Michèle
M
Dapas
Barbara
B
Farra
Rossella
R
Mizzau
Michela
M
Guarnieri
Gianfranco
G
Buiatti
Stefano
S
Giansante
Carlo
C
D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D001515:Beer; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D013695:Temperance
D000975:Antioxidants; D000431:Ethanol; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005978:Glutathione