Therapeutic use of miR-483 mimic for treating aortic valve clarification.
- MiR-483 or mimics of miR-483 could be used as a therapeutic.
- Could also be a target for additional drug development toward a non-invasive therapy for aortic valve calcification.
Aortic stenosis (AS) is the most common type of heart valve disease in the elderly, affecting 4.6% of people over the age of 75. AS is often caused by aortic valve calcification (AVC), a degenerative disease of the heart that causes narrowing of the aortic valve. As the population ages, AS and AVC become increasingly important public health problems. There is a need for a non-surgical, therapeutic approach to treat aortic valve calcification.
Aortic stenosis limits the amount of blood that can leave the valve and thus causes the heart to pump blood through the valve at an increased force, this is mainly caused by narrowing due to aortic valve calcification. Aortic valve calcification calcium deposits form on the aortic valve in the heart. Said deposits can cause narrowing at the opening of the aortic valve which can require valve repair surgery. Researchers at Emory have discovered that a differentially expressed, flow sensitive, microRNA (miRNAs) in the aorta and heat takes part in controlling inflammation and progressive calcification of the aortic valve. Using human endothelial cell lines, the researchers demonstrated that expression of miR-483 decreased under conditions of oscillatory flow. Furthermore, work was done to validate that ubiquitin E2 ligase expression is regulated by miR-483 which in regulates inflammation via degrading von-Hippel-Lindau tumor suppressor protein and then increasing expression of HIF1α thus leading to inflammation and progressive calcification.
Animal testing conducted.
- BMES Meeting, 10/12/2017
- Fernandez-Esmerats J, et al Arterioscler Thromb Vasc Biol. 2019;39(3):467-481. PMC6393167
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