Integrated analyses of Mendelian randomization, eQTL, and single-cell transcriptome identify CCN3 as a potential...

Area of Science:

• Biochemistry
• Genetics
• Cardiovascular Research

Background:

• Plasma secretory proteins are implicated in various diseases, including aortic dissection (AD).
• Existing research on plasma protein levels and AD lacks specificity.
• Identifying reliable biomarkers for AD is crucial for early detection and treatment.

Purpose of the Study:

• To explore plasma secretory proteins as potential diagnostic biomarkers for aortic dissection (AD).
• To identify specific genes and their protein products associated with AD risk.
• To investigate the functional role of identified proteins in AD pathogenesis.

Main Methods:

• Genome-wide association studies (GWAS) and expression quantitative trait locus (eQTL) analysis.
• Human plasma protein profiling and single-cell RNA sequencing.
• Quantitative PCR (qPCR) for mRNA analysis and ELISA for protein quantification.

Main Results:

• Identified high-risk genes (DBNL, NPC2, SUMF2, TFPI) and low-risk genes (CCN3, PRKCSH, TEX264, TGFBR3) for AD.
• CCN3 showed consistent downregulation in both mRNA and plasma levels in AD patients.
• Enrichment analysis suggested CCN3's involvement in focal adhesion and PI3K-Akt signaling.

Conclusions:

• CCN3 may serve as a protective factor in aortic dissection.
• Downregulation of CCN3 in AD is associated with altered cellular functions.
• Further research into CCN3's role could lead to novel therapeutic strategies for AD.