Lnc_000048 Promotes Histone H3K4 Methylation of MAP2K2 to Reduce Plaque Stability by Recruiting KDM1A in Carotid Atherosclerosis

Stabilizing and inhibiting plaque formation is a key challenge for preventing and treating ischemic stroke. KDM1A-mediated histone modifications, which involved in the development of training immunity, ultimately exacerbate the outcomes of inflammation. Although lncRNAs can recruit KDM1A to particip...

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Bibliographic Details
Published in:Molecular neurobiology 2023-05, Vol.60 (5), p.2572-2586
Main Authors: Zhang, Shuai, Sun, Yu, Xiao, Qi, Niu, Mengying, Pan, Xudong, Zhu, Xiaoyan
Format: Article
Language:English
Subjects:
Animals
Apolipoprotein E
Arteriosclerosis
Atherosclerosis
Biomedical and Life Sciences
Biomedicine
Carotid Artery Diseases
Cell Biology
Cell proliferation
Collagen
Histone Demethylases - metabolism
Histones
Histones - metabolism
Inflammation
Ischemia
MAP kinase
MAP Kinase Kinase 2 - metabolism
Methylation
Mice
Mice, Knockout, ApoE
Neurobiology
Neurology
Neurosciences
Non-coding RNA
Phosphorylation
Plaque, Atherosclerotic - metabolism
RNA, Long Noncoding - genetics
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Summary:Stabilizing and inhibiting plaque formation is a key challenge for preventing and treating ischemic stroke. KDM1A-mediated histone modifications, which involved in the development of training immunity, ultimately exacerbate the outcomes of inflammation. Although lncRNAs can recruit KDM1A to participate in histone methylation modification and regulate inflammation, cell proliferation, and other biological processes, little is known about the role of KDM1A-lncRNA interaction during atherosclerosis. The present study sought to delineate the effect of the interaction between lnc_000048 and KDM1A on plaque rupture in carotid atherosclerosis, as well as the potential mechanism. Our results revealed that lnc_000048 reduced the activity of histone demethylase and activated MAP2K2 expression by interacting with KDM1A. Furthermore, upregulated lnc_000048 indirectly regulated ERK phosphorylation by MAP2K2 and eventually activated the inflammatory response through the MAPK pathway, which was involved in atherosclerosis. Importantly, our study using ApoE-/- mice confirmed the regulatory role of lnc_000048 in promoting inflammation and collagen degradation in atherosclerotic plaques. These results suggest that targeting the lnc_000048 /KDM1A/MAP2K2/ERK axis may be a promising strategy for preventing atherosclerosis.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-023-03214-0