A regulatory role of novel long non-coding RNA, BAZ1A-AS1, in vascular smooth muscle cell functions during neointima formation in human saphenous veins

Kim, D. S.; Goo, B.; Veerapaneni, P.; Chouhaita, R.; Ogbi, M.; Fulton, D. J.; Zhang, W.; Long, X.; Guha, A.; Keeney, S.; Coffey, P.; Rice, R. D.; Gallo, D. R.; Patel, V. S.; Lee, R.; Kim, H. W.; Shi, H.; Weintraub, N. L.

doi:10.64898/2026.02.03.703576

bioRxiv · 10.64898/2026.02.03.703576

A regulatory role of novel long non-coding RNA, BAZ1A-AS1, in vascular smooth muscle cell functions during neointima formation in human saphenous veins

Kim, D. S.·Goo, B.·Veerapaneni, P.·Chouhaita, R.·Ogbi, M.·Fulton, D. J.·Zhang, W.·Long, X.·Guha, A.·Keeney, S.·Coffey, P.·Rice, R. D.·Gallo, D. R.·Patel, V. S.·Lee, R.·Kim, H. W.·Shi, H.·Weintraub, N. L.

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Abstract

BackgroundNeointimal proliferation (NP) is a major cause of stenosis and occlusion in arteries and veins. Human saphenous veins (HSV), often used for coronary artery bypass grafting, frequently fail in part due to NP. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of vascular smooth muscle cell (VSMC) phenotype, yet lncRNAs governing NP in human veins remain largely uncharacterized. Methods and ResultsUsing an ex vivo model of NP in human SV, we performed bulk RNA sequencing on SV tissues with and without NP. Among differentially expressed lncRNAs, we identified a previously uncharacterized transcript, Bromodomain Adjacent to Zinc Finger A1 antisense 1 (BAZ1A-AS1), and its predicted cis-regulatory partner gene BAZ1A, as markedly upregulated during NP and predominantly enriched in VSMCs. Both transcripts were induced by genotoxic stimuli, with BAZ1A-AS1 showing transient induction preceding sustained BAZ1A upregulation, consistent with a priming role in the DNA damage response. Silencing of either BAZ1A-AS1 or BAZ1A attenuated VSMC proliferation and migration, accompanied by upregulation of contractile markers and suppression of proliferative and inflammatory transcriptional programs. ChIRP-qPCR demonstrated that BAZ1A-AS1 physically interacts with 3' distal exons of BAZ1A at the DNA level while selectively engaging CNN1, CCND1, and IL6 mRNAs, indicating mechanistically distinct chromatin- and RNA-level regulatory functions. Baz1a haploinsufficiency attenuated neointima formation and preserved VSMC contractile identity in a mouse carotid artery ligation model. ConclusionsWe identify BAZ1A-AS1 and BAZ1A as stress-responsive regulators of VSMC phenotype, operating through dual mechanisms of cis-regulatory chromatin interaction and selective mRNA engagement, and demonstrate a novel role for the BAZ1A-AS1/BAZ1A axis in promoting NP.

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Kim, D. S., Goo, B., Veerapaneni, P., Chouhaita, R., Ogbi, M., Fulton, D. J., Zhang, W., Long, X., Guha, A., Keeney, S., Coffey, P., Rice, R. D., Gallo, D. R., Patel, V. S., Lee, R., Kim, H. W., Shi, H., Weintraub, N. L.. 2026-02-05. A regulatory role of novel long non-coding RNA, BAZ1A-AS1, in vascular smooth muscle cell functions during neointima formation in human saphenous veins. https://doi.org/10.64898/2026.02.03.703576

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