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Ann Med. 2017 Dec;49(8):661-677. doi: 10.1080/07853890.2017.1366041. Epub 2017 Aug 22.

Role of lipids and intraplaque hypoxia in the formation of neovascularization in atherosclerosis.

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a Department of Neurochemistry, Division of Basic and Applied Neurobiology , Serbsky Federal Medical Research Center of Psychiatry and Narcology , Moscow , Russia.
b Laboratory of Angiopathology , Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences , Moscow , Russia.
c Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology , Moscow , Russia.
d Institute for Atherosclerosis Research, Skolkovo Innovative Center , Moscow , Russia.


According to the current paradigm, chronic vascular inflammation plays a central role in the pathogenesis of atherosclerosis. The plaque progression is typically completed with rupture and subsequent acute cardiovascular complications. Previously, the role of adventitial vasa vasorum in atherogenesis was underestimated. However, investigators then revealed that vasa vasorum neovascularization can be observed when no clinical manifestation of atherosclerosis is present. Vasa vasorum is involved in various proatherogenic processes such as intimal accumulation of inflammatory leukocytes, intimal thickening, necrotic core formation, intraplaque haemorrhage, lesion rupture and atherothrombosis. Due to the destabilizing action of the intraplaque microenvironment, lesional vasa vasorum neovessels experience serious defects and abnormalities during development that leads to their immaturity, fragility and leakage. Indeed, intraplaque neovessels are a main cause of intraplaque haemorrhage. Visualization techniques showed that presence of neovascularization/haemorrhage can serve as a good indicator of lesion instability and higher risk of rupture. Vasa vasorum density is a strong predictor of acute cardiovascular events such as sudden death, myocardial infarction and stroke. At present, arterial vasa vasorum neovascularization is under intensive investigation along with development of therapeutic tools focused on the control of formation of vasa vasorum neovessels in order to prevent plaque haemorrhage/rupture and thromboembolism. KEY MESSAGE Neovascularization plays an important role in atherosclerosis, being involved in unstable plaque formation. Presence of neovascularization and haemorrhage indicates plaque instability and risk of rupture. Various imaging techniques are available to study neovascularization.


Vasa vasorum; angiogenic treatment; atherosclerosis; imaging technique; intraplaque haemorrhage; neovascularization; plaque rupture

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