Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation...

Area of Science:

• Cardiovascular Biology
• Molecular Mechanisms of Disease
• Transcriptional Regulation

Background:

• Calcific aortic valve disease (CAVD) is a primary cause of aortic stenosis, leading to severe cardiovascular complications.
• The intricate molecular and transcriptional regulatory mechanisms driving CAVD progression require further investigation.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying CAVD progression.
• To investigate the role of transcriptional regulation, specifically alternative polyadenylation (APA), in CAVD.
• To identify potential therapeutic targets for inhibiting calcium deposition in CAVD.

Main Methods:

• Utilized porcine valvular interstitial cells (PVICs) as an in vitro model for CAVD.
• Induced calcification using osteogenic induced medium (OIM) and subsequently treated with basic fibroblast growth factor (bFGF).
• Employed mRNA sequencing (mRNA-seq) and DaPars for transcriptome-wide analysis of gene expression and APA events.

Main Results:

• Successfully induced and inhibited calcium deposition in PVICs.
• Identified differentially expressed mRNAs and global APA events across control, OIM-induced, and bFGF-treated groups.
• Discovered that catalase (CAT) is a potential target regulated by bFGF-induced APA.

Conclusions:

• Described global APA changes in a model relevant to CAVD.
• Revealed that transcriptional regulation of the CAT gene may play a role in bFGF-mediated inhibition of calcium deposition.
• Highlighted CAT gene regulation as a potential therapeutic strategy for CAVD.