Metalloproteinases, Sialidases and NADPH Oxidases as Key Enzymes involved in Atherosclerosis Development

Background: Atherosclerosis and related cardiovascular diseases remain the leading cause of mortality and morbidity worldwide. Atherosclerosis development involves several pathological processes, including alterations of the blood lipid profile, chronic inflammation and thrombogenesis. The existing therapies for atherosclerosis are aimed at normalization of the lipid profile, reduction of cardiovascular risks and inflammation and alleviation of symptoms. Despite the certain progress made in the field, more efficient and direct approaches are needed to battle the disease effectively. Enzymes that are up-regulated or play key roles in various pathologies are traditionally regarded as potential therapeutic targets.

Methods and findings: We searched MEDLINE for recent articles reporting on the three enzymes that are involved in atherosclerosis development: matrix metallo-proteinases, neuraminidase/sialidases and NADPH oxidases. These enzymes participate in matrix remodeling, atherogenic modifications of LDL particles, and oxidative stress correspondingly.

Conclusion: The enzymes involved in atherosclerosis development, such as metalloproteinases, sialidases, and NADPH oxidases, appear to be potential therapeutic targets for the disease prevention and/or treatment. However, more selective and potent inhibitors of these enzymes need to be discovered before they become relevant for clinical treatment of atherosclerosis.

Author(s):

Anastasia V Poznyak, Dmitry A Kashirskikh, Victoria A Khotina, Andrey V Grechko and Alexander N Orekhov

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