Igor A. Sobenin, Alexander M. Markin*, Victor Y. Glanz, Yuliya V. Markina, Wei-Kai Wu, Veronika A. Myasoedova and Alexander N. Orekhov Pages 2438 - 2450 ( 13 )
The most typical feature of atherogenesis in humans at its early stage is the formation of foam cells in subendothelial arterial intima, which occurs as the consequence of intracellular cholesterol deposition. The main source of lipids accumulating in the arterial wall is circulating low-density lipoprotein (LDL). However, LDL particles should undergo proatherogenic modification to acquire atherogenic properties. One of the known types of atherogenic modification of LDL is enzymatic deglycosilation, namely, desialylation, which is the earliest change in the cascade of following multiple LDL modifications. The accumulating data make sialidases an intriguing and plausible therapeutic target, since pharmacological modulation of activity of these enzymes may have beneficial effects in several pathologies, including atherosclerosis. The hypothesis exists that decreasing LDL enzymatic desialylation may result in the prevention of lipid accumulation in arterial wall, thus breaking down one of the key players in atherogenesis at the cellular level. Several drugs acting as glycomimetics and inhibiting sialidase enzymatic activity already exist, but the concept of sialidase inhibition as an anti-atherosclerosis strategy remains unexplored to date. This review is focused on the potential possibilities of the repurposing of sialidase inhibitors for pathogenetic anti-atherosclerotic therapy.
Atherosclerosis, low density lipoprotein, atherogenic modification, deglycosylation, desialylation, intracellular cholesterol accumulation, sialidase inhibitors, drug repurposing.
Laboratory of Infection Pathology and Molecular Microecology & Central Laboratory of Pathology, Institute of Human Morphology, Moscow, Laboratory of Infection Pathology and Molecular Microecology & Central Laboratory of Pathology, Institute of Human Morphology, Moscow, Laboratory of Infection Pathology and Molecular Microecology & Central Laboratory of Pathology, Institute of Human Morphology, Moscow, Laboratory of Infection Pathology and Molecular Microecology & Central Laboratory of Pathology, Institute of Human Morphology, Moscow, Department of Internal Medicine, National Taiwan University Hospital, Bei- Hu Branch, Taipei, Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow