ИСТИНА

Atherosclerosis is an important medical and social problem. Cardiovascular diseases have become one of the leading causes of death and disability worldwide. Many of them, including ischemic stroke, myocardial infarction and sudden cardiac death are consequences of atherosclerosis development in major arteries. Atherogenesis includes several stages – accumulation of lipids in the vascular wall, inflammation and development of necrotic plaques with thin or thick fibrous cap. Despite intensive study, the initial phases of atherosclerotic plaque formation are poorly understood. It is well known fact that atherosclerosis usually develops in typical sites – curvatures and bifurcations of arteries, but the reasons for this have not been fully clarified. Atherogenic factors (age, obesity, dyslipidemia, hypertension, smoking) act systemically, so there must be a special mechanism of local atherogenesis induction. Shear stress plays a great role in this process, leading to changes in endothelial permeability and expression of different genes. However, there are relatively straight sections of vessels in humans in which atherosclerosis frequently occurs. Using immunohistochemistry and transgenic animals we showed possible cellular mechanisms of atherosclerosis mosaicism. Understanding of these mechanisms is extremely important for the creation of drugs that are effective at the initial stages of atherogenesis before the development of serious complications. Advanced atherosclerotic lesions are much more dangerous and therefore better studied. A sudden rupture of a plaque leads to thrombosis and the development of myocardial infarction or stroke, so the main goal in the treatment of atherosclerosis is to prevent such ruptures. Using a genetic approach, we identified key proteins whose activity leads to the rupture of an atherosclerotic plaque. Thus, our data not only contribute to a better understanding of atherogenesis but also can be used to create new generations of anti-atherosclerotic drugs. This research was fiancially supported by Russian Scientifi Foundation, project No 14-24-00086.