Tobacco inhibits a protective gene that keeps arteries healthy. The production of a protein linked to the formation of atherosclerosis is then promoted.
Cigarettes clog the arteries. A consequence of smoking linked to the inhibition of a protective gene, reveals a study published this Monday 1er May in the scientific journal Circulation.
By blocking the action of this gene, tobacco stimulates the synthesis of a molecule that promotes the formation of fatty plaque in the blood vessels, and thus increases the risk of developing coronary heart disease.
“Our conclusion suggests that inhibiting this enzyme would be particularly beneficial for smokers, but also for all people at high risk of cardiovascular pathologies,” explained Prof. Muredach Reilly, professor of cardiology at Columbia Medical University (States -United).
Millions of deaths
Globally, cigarettes are responsible for one in five cases of coronary heart disease and at least 1.6 million deaths each year. Despite this scourge, the scientific world had not yet discovered the mechanisms leading to the appearance of these disorders of the heart and vessels. Genetic predisposing factors have been mentioned in particular.
Professor Reilly’s team therefore got down to the genetic analysis of more than 140,000 people who participated in around 30 studies. The researchers particularly focused on 45 small regions of the genome known to be associated with an increased risk of coronary heart disease.
A variation and everything gets carried away
Analysis showed that a single change in the genetic code on chromosome 15 is associated with a 15% reduced risk of cardiovascular disease. This small variation was located close to a gene involved in the production of an enzyme called ADAMTS7 in the arteries. In contrast, smokers carrying this mutation only benefited from a 5% risk reduction.
Work carried out on mice has shown that by suppressing this gene, and therefore the production of this protein, the formation of atherosclerotic plaque in the arteries is avoided.
Another experiment carried out on cells making up the arteries also confirmed the protective role of this gene. When exposed to liquid cigarette extracts, cells overactivated the production of the ADAMTS7 enzyme to the point of doubling it.
A step towards precision medicine
“These results are an important step in solving the complex puzzle of the environment-gene interaction that leads to coronary heart disease,” said Prof. Danish Saleheen, head of the study and assistant professor of biostatistics and epidemiology at the university. from Pennsylvania.
In their next work, the researchers hope to understand how tobacco acts on this gene, and to determine whether inhibition of ADAMTS7 may slow the development of atherosclerosis induced by smoking.
“This study is an example of precision medicine, an emerging field. Thanks to these large genetic studies, we are starting to understand the impact of genetic variations on certain environmental factors or lifestyles, ”commented Professor Reilly.
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