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.

中文翻译：

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胰高血糖素样肽 1 减少与钙化性主动脉瓣疾病有关：GLP-1 抑制主动脉瓣间质细胞的钙化。

目的：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) 中的浓度和作用。背景：钙化性主动脉瓣疾病是一种以主动脉瓣变性和矿化为主要表现的慢性疾病。我们假设 GLP-1 的水平与 CAVD 相关并且它参与主动脉瓣间质细胞 (AVIC) 的钙化。方法：我们通过免疫组织化学 (IHC) 分析比较了 11 个钙化和 12 个正常主动脉瓣组织之间的 GLP-1 浓度。ELISA 用于测量 Control (n = 197) 和 CAVD 组 (n = 200) 血清中的 GLP-1。还表征了 GLP-1 对 AVIC 钙化和钙化基因表达调节的影响。结果：钙化主动脉瓣中的 GLP-1 浓度比对照非钙化主动脉瓣低 39%。在 CAVD 患者中，其血清浓度降低了 19.3%。多变量回归分析表明 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，它下调 RUNX2、MSX2、BMP2 和 BMP4 的表达，但上调 SOX9 的表达。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 的新治疗目标。多变量回归分析表明 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，它下调 RUNX2、MSX2、BMP2 和 BMP4 的表达，但上调 SOX9 的表达。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 的新治疗目标。多变量回归分析表明 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，它下调 RUNX2、MSX2、BMP2 和 BMP4 的表达，但上调 SOX9 的表达。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 的新治疗目标。GLP-1 通过调控特定的钙化基因参与 AVICs 的矿化。GLP-1 值得考虑作为 CAVD 的新治疗目标。GLP-1 通过调控特定的钙化基因参与 AVICs 的矿化。GLP-1 值得考虑作为 CAVD 的新治疗目标。