期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 96, 期 2, 页码 175-189出版社
WILEY
DOI: 10.1111/imcb.1028
关键词
Atherosclerosis; long noncoding RNA; matrix metalloproteinase 1; the low-density lipoprotein related receptor 2 binding protein
资金
- National Natural Sciences Foundation of China [81572051, 81472009, 81500387, 81672076]
- Natural Science Fund of Guangdong [2014A030313287, 2014 A030310135, 2015A030313245]
- Science and Technology Program of Guangzhou [201510010091, 201607010267, 201604020015]
- Foundation for National Outstanding Youth Fund Cultivation Plan of Nanfang Hospital [JQ201402]
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.
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