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| Pàgina inicial > Articles > Articles publicats > Identification of endoplasmic reticulum stress-associated lncRNAs influencing inflammation and VSMC function in abdominal aortic aneurysm |
(Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Universidad Rey Juan Carlos) (Institut de Recerca Sant Pau) (Universidad Rey Juan Carlos) (Universidad Rey Juan Carlos) (Institut de Recerca Sant Pau) (Universidad Autónoma de Madrid) (Universidad Rey Juan Carlos)
| Data: | 2025 |
| Resum: | Endoplasmic reticulum (ER) stress plays a critical role in the abdominal aortic aneurysm (AAA), a life-threatening disease characterized by inflammation, destructive remodeling, and vascular smooth muscle cells (VSMCs) dysfunction. The current therapy relies on surgical repair, but no effective pharmacological strategies are available to limit aneurysm progression. Long non-coding RNAs (lncRNAs) are essential factors in health and disease; however, their specific contribution to AAA development and its relationship with ER stress remain unexplored. Here, we have performed a whole-genome transcriptomic analysis characterizing the expression profile of lncRNAs in AAA. RNA sequencing was carried out in abdominal aorta from patients with AAA and healthy donors. We identified 6576 differentially expressed (DE)-mRNAs and 1283 DE-lncRNAs. Interestingly, bioinformatic analysis revealed a set of 368 DE-lncRNAs related to ER stress. The differential expression of the most induced lncRNAs (IL-21-AS1, ITPKB-IT, PCED1B-AS1, TCL-6, LINC00494, LINC00582, LINC00626, LINC00861, and LINC00892) was validated in a large cohort of patients with AAA. The ability of these selected lncRNAs to discriminate patients with AAA from healthy subjects was established by receiveroperating characteristic curves and logistic regression analysis. In human aortic VSMC and Jurkat T-cells, tunicamycin-induced ER stress triggered the expression of IL21-AS1, LINC00626, LINC00494, LINC00892, PCED1B-AS1, ITPKB-IT, and TCL-6, while tauroursodeoxycholic acid counteracted these effects. Finally, an integrated analysis of mRNA-lncRNA co-expression revealed the correlation between the selected lncRNAs and the DE-mRNAs involved in immune response and muscle contraction. Therefore, these DE-lncRNAs potentially implicated in the ER stress response, a pathological process in AAA, could be considered as potential therapeutic target to handle AAA. |
| Ajuts: | Instituto de Salud Carlos III PI20/01004 Instituto de Salud Carlos III PI21/01048 Agencia Estatal de Investigación PID2020116498RB-I00 Instituto de Salud Carlos III FI21/00125 Instituto de Salud Carlos III CP20/00013 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Aneurysm ; Aorta ; Endoplasmic reticulum stress ; Long non-coding RNA |
| Publicat a: | Clinical science (1979), Vol. 139 Núm. 6 (March 2025) , p. 357-372, ISSN 1470-8736 |
