Wedge by wedge
How does ethanol help the heart
Kirill Stasevich, "Science and Life", based on the materials of Medicalexpress: Research shows how a moderate dose of alcohol protects the heart
The fact that moderate doses of alcohol are good for health has been talked about for a long time. However, in most studies on this topic, one can only see a positive statistical correlation between alcohol consumption and health (or life expectancy); and most often they discuss at what age alcohol is useful, for whom exactly – for men or for women, and what is a moderate dose. But what about the mechanism by which it exerts its beneficial effect?
An article by researchers from the University of Sao Paulo in Cardiovascular Research (Ueta et al., Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde dehydrogenase 2) is devoted to just such a mechanism. Julio Ferreira and his colleagues experimented with mouse hearts, which were extracted from animals and kept in a viable state for some time by pumping a solution with oxygen and nutrients through them. An analogue of an ischemic attack was arranged for the heart, blocking the flow of the nutrient solution for half an hour; then the supply of the solution was resumed, but the heart was already beating slower, and if it was not helped to cope with stress in any way, about half of the heart cells simply died.
It is known that in such situations, the amount of 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde that damages intracellular structures, increases in the heart muscle. Usually its level is controlled by the enzyme ALDH2 (acetaldehyde dehydrogenase-2), which neutralizes all dangerous aldehydes, that is, not only 4-hydroxy-2-nonenal, but also, for example, acetaldehyde, which appears during the processing of ethanol in the liver. However, as the authors of the work showed earlier, with an ischemic attack, the activity of this enzyme drops significantly, and therefore there is too much nonenal.
As it turned out, the activity of the enzyme can be kept at a height with the help of ethyl alcohol. If alcohol was added to the nutrient solution for ten minutes before an artificial ischemic attack to the heart, then ALDH2 in the stressed heart worked twice as well as without alcohol, and not half, but 30% of the heart cells died. (The amount of ethanol corresponded to two glasses of wine for the average man – naturally, the dose was recalculated for male mice.)
When the activity of the enzyme was suppressed with the help of a special substance or a mutation was introduced into its gene, then, despite the portion of alcohol, the cells died, and more of them died – up to 70-80%, that is, alcohol only aggravated stress. But if such a mutant enzyme was artificially stimulated with the help of an experimental drug, the number of dead heart cells decreased to 35%.
In other words, the effect of ethanol on the heart depends on the enzyme ALDH2: if the enzyme works, moderate doses of alcohol will help the heart muscle overcome physiological troubles – under the action of acetaldehyde formed from ethanol, ALDH2 will remain active and rid the heart of dangerous nonenal. (Acetaldehyde itself is also unsafe, so it turns out that one garbage molecule helps to get rid of both itself and another garbage molecule.)
If the enzyme initially does not work well, then even moderate doses of ethanol can be dangerous. Accordingly, excessive doses will be dangerous in any case – even a normally functioning ALDH2 will not be able to cope with a large amount of acetaldehyde. However, the question remains how exactly acetaldehyde maintains the activity of ALDH2 under stress, and at the same time it would be good to clarify whether this biochemical mechanism works in an ordinary, healthy heart that is not in danger of an ischemic attack.
Nevertheless, some practical conclusions can be drawn from the results already now. Firstly, the mutation by which the enzyme was weakened is often found in people, especially in people from Southeast Asia, so in order to understand how much you can drink without fear for your heart, a person needs to find out which variant of the ALDH2 gene he got.
Secondly, medicinal substances that stimulate ALDH2 may be useful not only for the heart weakened by alcoholism, but also in the case of some other cardiac disorders.
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