Atherosclerosis

The early event in the formation of an atheroma plaque is the deposit of lipids in the wall of the arteries called lipid streaks, favored by the imbalance between food intake, the circulating rate and the elimination of cholesterol and also the abnormalities local blood flow, turbulence, hyperflow. These lipid deposits are eliminated by an inflammatory process but which eventually lead to the accumulation of cellular debris and the formation of the atheroma plaque which grows larger. The solidity of this plate is a major aspect of cardiovascular diseases, it depends on its degree of fibrosis, that is to say on the fibrous layer. Under certain conditions, enzymes, the proteases secreted by the cells of the inflammation, will digest the fibrosis, the screed will become fragile, the plaque will crack, erode with a risk of sudden formation of blood clots which can obstruct the lumen of the artery or migrate into the circulation in the form of emboli and become blocked in a small vessel. caliber, for example those of the brain.

Atherosclerosis is the field of medicine where the notion of prevention and personalized medicine takes on its full meaning. A distinction is made between primary prevention, which aims to prevent the appearance of symptoms and complications of the disease, and secondary prevention, which applies once the disease has declared itself to avoid its aggravation. In both cases, the first target is the fight against the risk factors of atherosclerosis, i.e. lifestyle and dietary abnormalities, tobacco, sedentary lifestyle, hypertension, diabetes, etc.

The therapeutic revolution for atherosclerosis came from the development of drugs that prevent the accumulation of cholesterol in the walls of the arteries, the central event in the formation and aggravation of atherosclerotic plaque.

Several therapeutic classes exist: statins, fibrates, ezetimibe, cholestyramine, alone or in combination. Statins thus lower the level of bad cholesterol (carried by LDL-c) by about 30% and reduce the risk of cardiovascular disease by 30 to 40%.

A new class of drugs was born, PCSK9 inhibitors resulting from a discovery by French (Catherine Boileaux) and French-speaking (Marianne Abi Fadel Lebanon, Nabil Seidah Canada) researchers. Extremely effective but still expensive and difficult to use, PCSK9 inhibitors are reserved for populations at high risk of vascular disease.

There is also the treatment of inflammation which has become an important target to avoid the progression of plaque and in particular the risk of cracking and erosion.

Research efforts in this area are still considerable, they aim to understand the mechanisms responsible for the natural history of atherosclerotic plaques, their weakening, their rupture and how blood clots are formed.

The IHU ICAN teams are major players in this field

• IHU researchers have been working for many years on cholesterol metabolism and the links between cholesterol and the activation of the inflammatory response. Other teams are studying how diabetes or obesity can be risk factors for cardiovascular disease.
• The ACTION group conducts major multicenter and international clinical trials on the treatment of cardiovascular diseases and in particular the risk of thrombosis
• The clinical teams are among the first in France for the management of these cardiovascular diseases.