Cardioprotective effects of alcohol: mediation by human vascular alcohol dehydrogenase.
Numerous studies have shown that moderate drinking protects against coronary disease, but no mechanism for this effect has been established. In the present study we show that the B1 isoenzyme of alcohol dehydrogenase (ADH) is expressed in human blood vessels. Polymerase chain reaction (PCR) employing total human aortic cDNA as a template detected a 0.6 kb band, the nucleotide sequence of which is an identical match to the low Km (50 microM) B1 ADH isoenzyme nucleotide sequence. Immunoblot of vascular homogenates shows a 40 KDa band, i.e., the size of the B1 ADH subunit, and immunohistochemical studies of vessel sections demonstrate high density staining with anti-human ADH (Class I) but not control sera. These studies identify within blood vessels the existence of a metabolic pathway sensitive to low substrate concentrations and capable of producing a reductive (NADH) environment that could antagonize lipoprotein oxidation and hence could account for a protective effect of ethanol on atherosclerosis.
Bello
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AT
Department of Medicine, St. Louis University Medical School, MO 63110.
Bora
N S
NS
Lange
L G
LG
Bora
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PS
D000426:Alcohol Dehydrogenase / Q000032:analysis / Q000096:biosynthesis*; D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001161:Arteriosclerosis / Q000517:prevention & control; D001483:Base Sequence; D001808:Blood Vessels / Q000201:enzymology; D015139:Blotting, Southern; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D017931:DNA Primers; D018076:DNA, Complementary / Q000302:isolation & purification; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression; D006736:Horses; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D016133:Polymerase Chain Reaction
D002316:Cardiotonic Agents; D017931:DNA Primers; D018076:DNA, Complementary; D007527:Isoenzymes; D000431:Ethanol; D000426:Alcohol Dehydrogenase