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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container_issue 2
container_start_page 175
container_title Immunology and cell biology
container_volume 96
creator 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
description 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.
doi_str_mv 10.1111/imcb.1028
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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.</description><identifier>ISSN: 0818-9641</identifier><identifier>EISSN: 1440-1711</identifier><identifier>DOI: 10.1111/imcb.1028</identifier><language>eng</language><ispartof>Immunology and cell biology, 2018-02, Vol.96 (2), p.175-189</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c748-42d031d91b5c4291e5410ffc470ca36c3465291ea035d9ba42d89318d40d82a23</citedby><cites>FETCH-LOGICAL-c748-42d031d91b5c4291e5410ffc470ca36c3465291ea035d9ba42d89318d40d82a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Zheng, Lei</creatorcontrib><creatorcontrib>Xu, Bang‐Ming</creatorcontrib><creatorcontrib>Tang, Wai‐Ho</creatorcontrib><creatorcontrib>Ye, Zhi‐Dong</creatorcontrib><creatorcontrib>Huang, Chuan</creatorcontrib><creatorcontrib>Ma, Xin</creatorcontrib><creatorcontrib>Zhao, Jing‐Jing</creatorcontrib><creatorcontrib>Guo, Feng‐Xia</creatorcontrib><creatorcontrib>Kang, Chun‐Min</creatorcontrib><creatorcontrib>Lu, Jing‐Bo</creatorcontrib><creatorcontrib>Xiu, Jian‐Cheng</creatorcontrib><creatorcontrib>Li, Pan</creatorcontrib><creatorcontrib>Xu, Yuan‐Jun</creatorcontrib><creatorcontrib>Xiao, Lei</creatorcontrib><creatorcontrib>Wu, Qian</creatorcontrib><creatorcontrib>Hu, Yan‐Wei</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><title>Lnc RNA ‐ RP 11‐714G18.1 suppresses vascular cell migration via directly targeting LRP 2 BP</title><title>Immunology and cell biology</title><description>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. 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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.</abstract><doi>10.1111/imcb.1028</doi><tpages>15</tpages></addata></record>
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title Lnc RNA ‐ RP 11‐714G18.1 suppresses vascular cell migration via directly targeting LRP 2 BP
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