ArticleCardiovascular research2025
Circular RNAs increase during vascular cell differentiation and are biomarkers for vascular disease.
Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Single cell analysis of developing Merkel cells reveals the emergence of non-coding RNA biotypes as a hallmark of terminal differentiation.Cell death and differentiation · 2026Article
- Multi-Omics and Machine Learning Integration Identifies Key Endothelial Modules in Carotid Artery Stenosis.Journal of clinical laboratory analysis · 2026Article
- Regulation of antiviral and antitumor immunity by theProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multiomics for Risk Stratification in Atherosclerotic Cardiovascular Disease.Circulation. Genomic and precision medicine · 2026Review
- Mechanosensitive snoRNA-like circular RNA sno-circCNOT1 drives endothelial dysfunction and atherosclerosis.Theranostics · 2026Article
- Establishing an atherosclerosis diagnostic model based on WGCNA and machine learning algorithms with key genes in cholesterol metabolism and ferroptosis, and revealing the regulatory role of HMOX1 in cellular ferroptosis.Frontiers in cardiovascular medicine · 2026Article
- circPVT1 regulates EMT and induces macrophage polarization to promotes the progression of renal cell carcinoma.Frontiers in immunology · 2026Article
- Machine learning and multi-omics technologies for precision cardiovascular medicine: advancing diagnosis, risk prediction, and therapeutic guidance.Frontiers in cardiovascular medicine · 2026Review
- Emerging Technologies for Exploring the Cellular Mechanisms in Vascular Diseases.International journal of molecular sciences · 2025Review
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Authors and funding
23 authors.
Funding
Abstract
aimsThe role of circular RNAs (circRNAs) and their regulation in health and disease are poorly understood. Here, we systematically investigated the temporally resolved transcriptomic expression of circRNAs during differentiation of human induced pluripotent stem cells (iPSCs) into vascular endothelial cells (ECs) and smooth muscle cells (SMCs) and explored their potential as biomarkers for human vascular disease. METHODS AND
resultsUsing high-throughput RNA sequencing and a de novo circRNA detection pipeline, we quantified the daily levels of 31 369 circRNAs in a 2-week differentiation trajectory from human stem cells to proliferating mesoderm progenitors to quiescent, differentiated EC and SMC. We detected a significant global increase in RNA circularization, with 397 and 214 circRNAs up-regulated greater than two-fold (adjusted P < 0.05) in mature EC and SMC, compared with undifferentiated progenitor cells. This global increase in circRNAs was associated with up-regulation of host genes and their promoters and a parallel down-regulation of splicing factors. Underlying this switch, the proliferation-regulating transcription factor MYC decreased as vascular cells matured, and inhibition of MYC led to down-regulation of splicing factors such as SRSF1 and SRSF2 and changes in vascular circRNA levels. Examining the identified circRNAs in arterial tissue samples and in peripheral blood mononuclear cells (PBMCs) from patients, we found that circRNA levels decreased in atherosclerotic disease, in contrast to their increase during iPSC maturation into EC and SMC. Using machine learning, we determined that a set of circRNAs derived from COL4A1, COL4A2, HSPG2, and YPEL2 discriminated atherosclerotic from healthy tissue with an area under the receiver operating characteristic curve (AUC) of 0.79. circRNAs from HSPG2 and YPEL2 in blood PBMC samples detected atherosclerosis with an AUC of 0.73.
conclusionTime-resolved transcriptional profiling of linear and circRNA species revealed that circRNAs provide granular molecular information for disease profiling. The identified circRNAs may serve as blood biomarkers for atherosclerotic vascular disease.
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