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Cardioprotective effects of alcohol: mediation by human vascular alcohol dehydrogenase
A T Bello1, N S Bora, L G Lange
1Department of Medicine, St. Louis University Medical School, MO 63110.
Insights
Moderate alcohol consumption may protect against coronary heart disease. This study found alcohol dehydrogenase (ADH) in human blood vessels, suggesting a mechanism for this protective cardiovascular effect.
Area of Science:
- Cardiovascular Biology
- Enzymology
- Molecular Biology
Background:
- Moderate alcohol consumption is linked to reduced coronary heart disease risk.
- The underlying biological mechanism for this cardioprotective effect remains unclear.
Purpose of the Study:
- To investigate the presence and function of alcohol dehydrogenase (ADH) in human blood vessels.
- To elucidate a potential mechanism for the protective effects of ethanol on atherosclerosis.
Main Methods:
- Polymerase chain reaction (PCR) on human aortic cDNA to detect ADH gene expression.
- Immunoblotting of vascular homogenates to identify ADH protein presence and size.
- Immunohistochemical analysis of human vessel sections to localize ADH expression.
Main Results:
- The B1 isoenzyme of alcohol dehydrogenase (ADH) was detected in human aortic cDNA via PCR.
- Immunoblotting confirmed the presence of a 40 KDa band, consistent with B1 ADH subunit size, in vascular homogenates.
- Immunohistochemistry showed significant staining for ADH (Class I) in human blood vessel sections.
Conclusions:
- Human blood vessels express the B1 isoenzyme of alcohol dehydrogenase (ADH).
- This suggests a local metabolic pathway in vasculature sensitive to ethanol.
- The pathway may produce a reductive environment, potentially antagonizing lipoprotein oxidation and explaining ethanol's protective effect against atherosclerosis.
Abstract:
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.