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

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

doi:10.3389/fcvm.2021.709741

Abstract

Objectives: This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD).Background: Calcific aortic valve disease 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 (AVICs).Methods: We compared the concentration of GLP-1 between 11 calcific and 12 normal aortic valve tissues by immunohistochemical (IHC) analysis. ELISA was used to measure GLP-1 in serum of the Control (n = 197) and CAVD groups (n = 200). The effect of GLP-1 on the calcification of 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 serum was 19.3% lower in CAVD patients. Multivariable regression analysis demonstrated that GLP-1 level was independently associated with CAVD risk. In vitro, GLP-1 antagonized AVIC calcification in a dose- and time-dependent manner and it down-regulated RUNX2, MSX2, BMP2, and BMP4 expression but up-regulated SOX9 expression.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.

Highlights

Glucagon-like peptide-1 (GLP-1), a hormone of 30 amino acids, is derived from proglucagon [1]
The IHC analysis showed that GLP-1 was mainly evenly distributed in the rich region of Valve interstitial cells (VICs) of control aortic valves, but GLP-1 was prominently distributed in the non-mineralized areas of calcific aortic valves (Figure 2A)
Based on the GLP-1 concentration of patients’ serum in this study (Table 2), we treated aortic valve interstitial cells (AVICs) with different doses of GLP-1 to identify the effect of GLP-1 on calcification in vitro

Summary

Introduction

Glucagon-like peptide-1 (GLP-1), a hormone of 30 amino acids, is derived from proglucagon [1]. It can increase insulin’s sensitivity in regulating blood glucose [2], which is an effect that partially reverses aging-related degenerative disease [3]. Calcific aortic valve disease involves chronic inflammatory responses [6], lipid accumulation [7, 8], extracellular matrix rebuilding [9, 10], and osteogenic-related gene activation [11, 12]. We hypothesized that the level of GLP-1 is associated with CAVD and that it participates in the calcification of aortic valve interstitial cells (AVICs)

Objectives

Methods

Results

Conclusion