Xiao Fan, Zha Qing, Zhang Qianru, Wu Qihong, Chen Zhongli, Yang Ying, Yang Ke, Liu Yan
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Vascular and Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2021 Aug 26;8:709741. doi: 10.3389/fcvm.2021.709741. eCollection 2021.
This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD). 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). 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 ( = 197) and CAVD groups ( = 200). The effect of GLP-1 on the calcification of AVICs and the regulation of calcific gene expression were also characterized. 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. , 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. 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.
本研究探讨胰高血糖素样肽-1(GLP-1)在钙化性主动脉瓣疾病(CAVD)中的浓度及作用。钙化性主动脉瓣疾病是一种表现为主动脉瓣退变和矿化的慢性疾病。我们假设GLP-1水平与CAVD相关,且它参与主动脉瓣间质细胞(AVICs)的钙化过程。我们通过免疫组织化学(IHC)分析比较了11个钙化主动脉瓣组织和12个正常主动脉瓣组织中GLP-1的浓度。采用酶联免疫吸附测定(ELISA)法检测对照组(n = 197)和CAVD组(n = 200)血清中的GLP-1。还对GLP-1对AVICs钙化的影响及钙化相关基因表达的调控进行了表征。钙化主动脉瓣中GLP-1的浓度比对照非钙化主动脉瓣低39%。CAVD患者血清中其浓度低19.3%。多变量回归分析表明,GLP-1水平与CAVD风险独立相关。此外,GLP-1以剂量和时间依赖性方式拮抗AVICs钙化,下调RUNX2、MSX2、BMP2和BMP4的表达,但上调SOX9的表达。GLP-1水平降低与CAVD相关,且GLP-1通过调节特定钙化基因参与AVICs的矿化过程。GLP-1有望成为CAVD的新型治疗靶点。