Lnc RNA ‐ RP 11‐714G18.1 suppresses vascular cell migration via directly targeting LRP 2 BP

Atherosclerotic cardiovascular disease is considered as the leading cause of mortality and morbidity worldwide. Accumulating evidence supports an important role for long noncoding RNA (lnc RNA ) in the pathogenesis of atherosclerosis. Nevertheless, the role of lnc RNA in atherosclerosis‐associated v...

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Veröffentlicht in:Immunology and cell biology 2018-02, Vol.96 (2), p.175-189
Hauptverfasser: Zhang, Yuan, Zheng, Lei, Xu, Bang‐Ming, Tang, Wai‐Ho, Ye, Zhi‐Dong, Huang, Chuan, Ma, Xin, Zhao, Jing‐Jing, Guo, Feng‐Xia, Kang, Chun‐Min, Lu, Jing‐Bo, Xiu, Jian‐Cheng, Li, Pan, Xu, Yuan‐Jun, Xiao, Lei, Wu, Qian, Hu, Yan‐Wei, Wang, Qian
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Sprache:eng
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Zusammenfassung:Atherosclerotic cardiovascular disease is considered as the leading cause of mortality and morbidity worldwide. Accumulating evidence supports an important role for long noncoding RNA (lnc RNA ) in the pathogenesis of atherosclerosis. Nevertheless, the role of lnc RNA in atherosclerosis‐associated vascular dysfunction and the underlying mechanism remain elusive. Here, using microarray analysis, we identified a novel lnc RNA RP 11‐714G18.1 with significant reduced expression in human advanced atherosclerotic plaque tissues. We demonstrated in both human vascular smooth muscle cells ( VSMC s) and endothelial cells ( EC s) that RP 11‐714G18.1 impaired cell migration, reduced the adhesion of EC s to monocytes, suppressed the neoangiogenesis, decreased apoptosis of VSMC s and promoted nitric oxide production. Mechanistically, RP 11‐714G18.1 could directly bind to its nearby gene LRP 2 BP and increased the expression of LRP 2 BP . Moreover, we showed that RP 11‐714G18.1 impaired cell migration through LRP 2 BP ‐mediated downregulation of matrix metalloproteinase ( MMP )1 in both EC s and VSMC s. In atherosclerotic patients, the serum levels of LRP 2 BP were positively correlated with high‐density lipoprotein cholesterol, but negatively correlated with cardiac troponin I. Our study suggests that RP 11‐714G18.1 may play an athero‐protective role by inhibiting vascular cell migration via RP 11‐714G18.1/ LRP 2 BP / MMP 1 signaling pathway, and targeting the pathway may provide new therapeutic approaches for atherosclerosis.
ISSN:0818-9641
1440-1711
DOI:10.1111/imcb.1028