Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells.
Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells.
复制标题
胰高血糖素样肽-1 减少与钙化主动脉瓣疾病相关：GLP-1 抑制主动脉瓣间质细胞钙化。
DOI：
10.3389/fcvm.2021.709741
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发表时间：
2021
影响因子：
3.6
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Xiao F;Zha Q;Zhang Q;Wu Q;Chen Z;Yang Y;Yang K;Liu Y
目的：探讨胰高血糖素样肽-1（GLP-1）在钙化性主动脉瓣疾病（CAVD）中的浓度和作用。背景：钙化性主动脉瓣疾病是一种以主动脉瓣退行性变和矿化为主要表现的慢性疾病。我们假设GLP-1水平与CAVD相关，并参与主动脉瓣间质细胞（AVIC）的钙化。方法：采用免疫组化（IHC）方法，对11例钙化和12例正常主动脉瓣组织中GLP-1的表达进行比较。采用ELISA法检测对照组（n = 197）和CAVD组（n = 200）血清中GLP-1水平。GLP-1对AVIC钙化的作用和钙化基因表达的调节也被表征。结果：钙化主动脉瓣中GLP-1浓度比对照非钙化主动脉瓣低39%。CAVD患者血药浓度降低19.3%。多因素回归分析显示GLP-1水平与CAVD风险独立相关。在体外，GLP-1以剂量和时间依赖性方式拮抗AVIC钙化，下调RUNX 2、MSX 2、BMP 2和BMP 4表达，但上调SOX 9表达。结论：GLP-1的减少与CAVD相关，GLP-1通过调节特定的钙化基因参与AVIC的矿化。GLP-1值得考虑作为CAVD的新治疗靶点。
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.