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Immunol Cell Biol. 2018 Feb;96(2):175-189. doi: 10.1111/imcb.1028. Epub 2017 Dec 7.

LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting LRP2BP.

Author information

1
Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
2
Clinical laboratory department, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, China.
3
Department of Cardiovascular Surgery, China- Japan Friendship Hospital, Beijing, 100029, China.
4
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
5
Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
6
Department of Cardiology, Nanfang Hospital, Southern medical University, Guangzhou, 510515, China.

Abstract

Atherosclerotic cardiovascular disease is considered as the leading cause of mortality and morbidity worldwide. Accumulating evidence supports an important role for long noncoding RNA (lncRNA) in the pathogenesis of atherosclerosis. Nevertheless, the role of lncRNA in atherosclerosis-associated vascular dysfunction and the underlying mechanism remain elusive. Here, using microarray analysis, we identified a novel lncRNA RP11-714G18.1 with significant reduced expression in human advanced atherosclerotic plaque tissues. We demonstrated in both human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) that RP11-714G18.1 impaired cell migration, reduced the adhesion of ECs to monocytes, suppressed the neoangiogenesis, decreased apoptosis of VSMCs and promoted nitric oxide production. Mechanistically, RP11-714G18.1 could directly bind to its nearby gene LRP2BP and increased the expression of LRP2BP. Moreover, we showed that RP11-714G18.1 impaired cell migration through LRP2BP-mediated downregulation of matrix metalloproteinase (MMP)1 in both ECs and VSMCs. In atherosclerotic patients, the serum levels of LRP2BP were positively correlated with high-density lipoprotein cholesterol, but negatively correlated with cardiac troponin I. Our study suggests that RP11-714G18.1 may play an athero-protective role by inhibiting vascular cell migration via RP11-714G18.1/LRP2BP/MMP1 signaling pathway, and targeting the pathway may provide new therapeutic approaches for atherosclerosis.

KEYWORDS:

Atherosclerosis; long noncoding RNA; matrix metalloproteinase 1; the low-density lipoprotein related receptor 2 binding protein

PMID:
29363163
DOI:
10.1111/imcb.1028
[Indexed for MEDLINE]

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