AUTHOR=Xiao Fan , Zha Qing , Zhang Qianru , Wu Qihong , Chen Zhongli , Yang Ying , Yang Ke , Liu Yan 

TITLE=Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.709741

DOI=10.3389/fcvm.2021.709741

ISSN=2297-055X

ABSTRACT=Objectives: This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD).
Background: CAVD is a chronic disease presenting with aortic valve degeneration and mineralization. We hypothesized that the level of GLP-1 is associated with CAVD and that it participates in the calcification of aortic valve interstitial cells.
Methods: We compared the concentration of GLP-1 between 11 calcific and 12 normal aortic valve tissues by immunohistochemical analysis. ELISA was used to measure GLP-1 in plasma of the Control (n=197) and CAVD groups (n=200). The effect of GLP-1 on the calcification of aortic valve interstitial cells (AVICs) and the regulation of calcific gene expression were also characterized.
Results: The GLP-1 concentration in the calcific aortic valves was 39% less than that in the control non-calcified aortic valves. Its concentration in plasma was 19.3% lower in CAVD patients. Multivariable regression analysis demonstrated that GLP-1 was an independent risk factor associated with CAVD. In vitro, GLP-1 antagonized AVIC calcification in a dose- and time-dependent manner and down-regulated RUNX2, MSX2, BMP2 and BMP4 but up-regulated SOX9. 
Conclusions: A reduction in GLP-1 was associated with CAVD, and GLP-1 participated in the mineralization of AVICs by regulating specific calcific genes. GLP-1 warrants consideration as a novel treatment target for CAVD.

Keywords: glucagon-like peptide-1, calcific aortic valve disease, aortic valve interstitial cells, calcification, age