Key result
Downregulated circulating miR-199a-3p and miR-26b-5p are linked to CAVD with AUC >0.62.
Why the study?
Are circulating miR-199a-3p and miR-26b-5p associated with endothelial ILK deficiency and calcific aortic valve disease?
Case-Control (n=90)
Are circulating miR-199a-3p and miR-26b-5p associated with endothelial ILK deficiency and calcific aortic valve disease?
Effect estimate: AUC >0.62
p-value: p=<0.05
Circulating miR-199a-3p and miR-26b-5p are downregulated in endothelial ILK deficiency and CAVD, suggesting their potential utility as biomarkers for monitoring CAVD progression.
Calcific aortic valve disease (CAVD) is the most common valvular heart disease worldwide, characterized by endothelial dysfunction, lipid accumulation, and inflammation, ultimately leading to calcification. We previously demonstrated that reduced integrin-linked kinase (ILK) expression in the aortic valve endothelium contributes to disease progression by promoting endothelial-to-osteoblastic differentiation. However, no biomarkers are currently available to detect endothelial ILK reduction. We utilized a conditional endothelial ILK knockout murine model (ecILKcKO) to investigate aortic valve calcification and identify potential circulating microRNAs (miRNAs) as biomarkers for CAVD. ecILKcKO mice exhibited increased expression of calcification markers (OSX, OPN, RUNX2) at three weeks (p<0.05) and significant fibrosis and valve leaflet thickening (p<0.01). However, pronounced valve deterioration emerged at twelve weeks post-ILK deletion, with increased peak aortic valve velocity (p<0.0001) and calcium deposit formation. Following confirmation of CAVD development in this model, we conducted RNA sequencing to analyze circulating miRNAs and compared these findings with miRNA profiles from CAVD patients. Notably, miR-199a-3p and miR-26b-5p were significantly downregulated in both ecILKcKO mice and CAVD patients. Validation in twelve-week-old ecILKcKO mice confirmed decreased circulating miR-199a-3p (p<0.01) and miR-26b-5p (p<0.05), mirroring results in CAVD patients (n=60) versus non-CAVD controls (n=30) (p<0.05). ROC curve analysis revealed AUC>0.62 (p<0.05) for both miRNAs in human samples. Our findings suggest that circulating miR-199a-3p and miR-26b-5p are sensitive to endothelial ILK reduction and disease presence, positioning them as potential biomarkers for monitoring CAVD progression. The availability of the ecILKcKO model provides a valuable platform for further validation and mechanistic studies.
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Delgado-Marín et al. (2025) conducted a case-control in Calcific aortic valve disease (CAVD) (n=90). Calcific aortic valve disease vs. Non-CAVD controls was evaluated on Circulating miR-199a-3p and miR-26b-5p levels (AUC >0.62, p=<0.05). Circulating miR-199a-3p and miR-26b-5p were significantly downregulated in CAVD patients compared to controls, with an AUC >0.62 (p<0.05) for both miRNAs.
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