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Volume 5
Journal of Current Research: Cardiology
Heart Congress 2018
November 21-22, 2018
2
nd
Global Heart Congress
November 21-22, 2018 Osaka, Japan
MicroRNA-22 promotes the osteogenic differentiation of valvular interstitial cells by targeting calcium
binding protein 39
Fan Yang
1
,
2
, Suxuan Liu
1
, Guokun Wang
1
and Jianxin Sun
2
1
Second Military Medical University, China
2
Thomas Jefferson University, USA
C
alcific Aortic Valve Disease (CAVD) is a complex pathological process for which no effective therapies currently exist.
Transformation of Valvular Interstitial Cells (VICs) to osteoblasts is believed to be one of the most important causes of valve
calcification. Recently, emerging evidence suggests that pro-osteogenic MicroRNAs play essential roles in the calcification of the
aortic valve. The purpose of this study is to determine whether miR-22 is critically involved in the osteogenic differentiation of VICs
and if so, to determine the molecular mechanisms involved. A total of 33 CAVD patients were enrolled in the study. The severity of
CAVD was determined by standard echocardiographic methods. To identify the aberrant expression of miRNAs in calcified aortic
valve, real-time PCR was performed to detect the expression profiles of osteogenic miRNAs in CAVD patients. Subsequently, we
identified miR-22 as one of the most significantly up-regulated miRNAs in calcified aortic valves. Fluorescence
in situ
hybridization
assay showed that miR-22 was expressed throughout the regions of the calcified valves and predominantly localized in VICs, as
indicated by the co-expression of vimentin. Elevated miR-22 levels were positively correlated with the expression of OPN (rs=0.820,
P<0.01) and Runx2 (rs=0.563, P<0.01) as well as VIC osteogenic differentiation. Furthermore, we identified calcium binding protein
39 (CAB39) as a novel downstream target of miR-22 in VICs, as determined by dual-luciferase reporter assay, real-time PCR
(Polymerase Chain Reaction) and western blot assays. Furthermore, we found that the CAB39 expression was negatively correlated
with the calcification severity in clinical CAVD samples, as determined by immunohistochemical staining analysis. Adenovirus-
mediated both gain- and loss-of-function analyses demonstrated that miR-22 is critically involved in the osteogenic differentiation of
VICs, specifically through regulating the CAB39-AMPK-mTOR signaling pathway. MicroRNA-22 serves as a potential inducer of
CAVD through inhibiting the CAB39/AMPK/mTOR signaling pathway. These results suggest that miR-22 may serve as a potential
therapeutic target for the calcific aortic valve disease.
dearwgk@163.comCurr Res Cardiol 2018, Volume 5
DOI: 10.4172/2368-0512-C1-003