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 |
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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. |
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ISSN: | 0818-9641 1440-1711 |
DOI: | 10.1111/imcb.1028 |