Abstract: Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions. However, the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear. Long non-coding RNAs (lncRNAs) have been shown to influence the occurrence and development of these lesions. We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing. To investigate the mechanism by which lnc_011797 regulates white matter lesions, we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions. The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses. Our findings indicate that lnc_011797 promoted ferroptosis in these cells, leading to the formation of white matter lesions. Furthermore, lnc_011797 functioned as a competitive endogenous RNA (ceRNA) for miR-193b-3p, thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins. To validate the role of lnc_011797 in vivo, we established a mouse model of white matter lesions through bilateral common carotid artery stenosis. The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions. These findings clarify the mechanism by which lncRNAs regulate white matter lesions, providing a new target for the diagnosis and treatment of white matter lesions.

Key words: bilateral common carotid artery stenosis, competing endogenous , RNA, exosome, ferroptosis, human umbilical vein endothelial cells, long noncoding RNAs, miR-193b-3p, oxygen-glucose deprivation, white matter lesions, WNK1