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Use of miRNA-483 and its Target Genes in Treatment of Cardiovascular and Inflammatory Diseases
Emory University
Nucleotide
Cardiovascular disease
Target Identification or Validation
• The miR-483 target, UBE2C, regulates the pVHL and HIF1α pathway, leading to endothelial inflammation, EndMT, and subsequent AV calcification.
• miR-483 mimic and HIF1α inhibitors may serve as potential therapeutics to reduce CAVD.
• 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.
• 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, Inventors demonstrated that expression of miR-483 decreased under conditions of oscillatory flow.
• 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.
US20220090079A1
Disturbed flow increases UBE2C via loss of miR-483-3p, inducing aortic valve calcification by the HIF1α pathway in endothelial cells. Arterioscler Thromb Vasc Biol. (2019)
