Identification of miR-143 as a Major Contributor for Human Stenotic Aortic Valve Disease.
Calcification of aortic valves leads to aortic stenosis mainly in elderly individuals, but the underlying molecular mechanisms are still not understood. Here, we studied microRNA (miR, miRNA) expression and function in healthy and stenotic human aortic valves. We identified miR-21, miR-24, and miR-143 to be highly upregulated in stenotic aortic valves. Using luciferase reporter systems, we found direct binding of miR-143 to the 3'UTR region of the matrix gla protein (MGP), which in turn is a key factor to sustain homeostasis in aortic valves. In subsequent experiments, we demonstrated a therapeutic potential of miRNA regulation during calcification in cardiac valvular interstitial cells. Collectively, our data provide evidence that deregulated miR expression contributes to the development of stenotic valve disease and thus form novel therapeutic opportunities of this severe cardiovascular disease.
['Fiedler|Jan|J|0000-0002-8855-2883', 'Park|Da-Hee|DH|', 'Hobuß|Lisa|L|', 'Anaraki|Parnian Kalbasi|PK|', 'Pfanne|Angelika|A|', 'Just|Annette|A|', 'Mitzka|Saskia|S|', 'Dumler|Inna|I|', 'Weidemann|Frank|F|', 'Hilfiker|Andres|A|', 'Thum|Thomas|T|']
D020413:3' Untranslated Regions D000368:Aged D000369:Aged, 80 and over D000818:Animals D001021:Aortic Valve D001024:Aortic Valve Stenosis D001665:Binding Sites D002114:Calcinosis D002135:Calcium-Binding Proteins D016022:Case-Control Studies D002478:Cells, Cultured D016326:Extracellular Matrix Proteins D005260:Female D006801:Humans D008297:Male D035683:MicroRNAs D010012:Osteogenesis D015398:Signal Transduction D034421:Sus scrofa D015854:Up-Regulation
microRNA Calcium deposition dependent on miR-143 Human aortic stenosis miR signature in aortic stenosis