Department of Cardiovascular Surgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
BMC Cardiovasc Disord. 2024 Feb 28;24(1):128. doi: 10.1186/s12872-024-03775-5.
Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated.
This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups.
We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation.
We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.
钙化性主动脉瓣疾病（CAVD）是导致心绞痛、心力衰竭和主动脉瓣狭窄死亡的主要原因。然而，其进展的分子机制，特别是复杂的疾病相关转录调控机制，仍有待进一步阐明。
本研究以猪瓣膜间质细胞（PVIC）为模型。我们使用成骨诱导培养基（OIM）诱导 PVIC 钙沉积，使其钙化，然后用碱性成纤维细胞生长因子（bFGF）处理以抑制钙沉积。使用转录组测序研究 PVIC 的 mRNA 表达谱及其相关的转录调控。我们使用 DaPars 进一步检查不同处理组之间的可变多聚腺苷酸化（APA）。
我们成功地通过 OIM 诱导了 PVIC 的钙沉积。随后，使用 mRNA-seq 鉴定了三种不同处理方式（对照、OIM 诱导和 OIM 诱导 bFGF 处理）的差异表达 mRNAs。通过生物信息学分析在 OIM 和 bFGF 处理组中鉴定了全局 APA 事件。最后，发现并证明过氧化氢酶（CAT）是 bFGF 诱导 APA 调节的潜在靶标之一。
我们描述了与 CAVD 相关的钙沉积模型中的全局 APA 变化。我们揭示了 CAT 基因的转录调控可能有助于 bFGF 诱导的钙沉积抑制。
