Circular RNAs increase during vascular cell differentiation and are biomarkers for vascular disease.
Summary
Daily RNA-seq across iPSC differentiation showed a global rise in circularization tied to MYC downregulation and reduced splicing factors. In patients, select circRNAs fell in atherosclerotic tissue and PBMCs, and a small panel (COL4A1/2, HSPG2, YPEL2) discriminated disease with AUC 0.79 in tissue and 0.73 in blood.
Key Findings
- Global circRNA levels increased during EC and SMC maturation with 397 and 214 circRNAs upregulated >2-fold (adjusted P<0.05).
- MYC decreased during maturation, paralleled by downregulation of splicing factors (e.g., SRSF1, SRSF2) and altered circRNA levels.
- In patients, circRNAs decreased in atherosclerotic tissue and PBMCs; a panel from COL4A1/COL4A2/HSPG2/YPEL2 discriminated disease (tissue AUC 0.79; PBMC AUC 0.73).
Clinical Implications
CircRNA panels could evolve into noninvasive blood tests for atherosclerosis detection or risk stratification; assays require standardization and prospective validation.
Why It Matters
Links developmental circRNA dynamics to disease signatures and provides a tangible, minimal circRNA panel with cross-tissue diagnostic potential.
Limitations
- Clinical validation cohorts and outcomes were limited; no prospective prognostic evaluation
- Causality between MYC/splicing changes and circRNA biogenesis not proven in vivo
Future Directions
Prospective, multi-center validation of circRNA panels, assay standardization, and mechanistic in vivo studies linking circRNA biogenesis to vascular remodeling and outcomes.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- III - Non-randomized case-control/mechanistic biomarker discovery with patient samples
- Study Design
- OTHER