Understanding the Genetic Mutation Behind Coronary Heart Disease: Atherosclerosis and the Role of the ACTA2 Gene

2023-07-10 16:00:00

Coronary heart disease is usually caused by a buildup of cholesterol in the coronary arteries. They appear around the age of 60, but sometimes they occur in young people with normal cholesterol levels and no risk factors. These cases question scientists, but a new study provides an explanation: in thirty-somethings, coronary heart disease is the result of a genetic mutation. The results of this work are published in European Heart Journal.

What is atherosclerosis?

Coronary artery disease, called atherosclerosis, is an accumulation of fats, cholesterol and other substances in and on the walls of the arteries. “It can develop over time and most people don’t know they have it until they have a heart attack or stroke,” the study authors said. , researchers at the University of Texas. The traditional risk factors are high cholesterol, high blood pressure, diabetes, smoking, obesity, lack of physical exercise and a diet high in fat.”

Atherosclerosis: what is the role of the ACTA2 gene?

As early as 2009, a study showed that variations in the ACTA2 gene might increase the risk of developing the disease in young people. This gene is found in the muscle cells that line the arteries and allow them to contract to control blood pressure and flow. “If there is a mutation, the protein encoded by this gene is not folded correctly and this triggers stress in the muscle cell, which then forces it to make more cholesterol internally, regardless of the cholesterol level in the blood, leading to the formation of atherosclerotic plaques”, specify the authors of this study.
In their work, they genetically modified a mouse to carry a mutation in the ACTA2 gene. The researchers fed these animals a diet high in cholesterol, which induced atherosclerosis. This confirmed the observation of their predecessor: these mice suffered much more from atherosclerosis than those who had not had the genetic modification but who followed the same diet.

A track of treatment once morest atherosclerosis in young subjects

The study also shows that this increase in atherosclerosis can be reversed by treating the mice with pravastatin, a molecule from the group of statins commonly prescribed to lower blood cholesterol. “In people with the ACTA2 gene mutation, statins block cholesterol produced by stressed muscle cells,” says Dianna Milewicz, lead author of this study. According to her, it might be useful to perform cardiac imaging in people with the genetic mutation, in order to start treatment with statins early enough. If left untreated, atherosclerosis can have serious complications. The rupture of the plaques can generate a clot, responsible for a heart attack or a cerebrovascular accident. It is the cause of 80% of sudden deaths according to theInserm.

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