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http://dx.doi.org/10.14348/molcells.2018.0162

Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model  

Zhang, Zhidong (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Zou, Gangqiang (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Chen, Xiaosan (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Lu, Wei (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Liu, Jianyang (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Zhai, Shuiting (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Qiao, Gang (Department of Vascular and Endovascular Surgery, Henan Provincial People's Hospital)
Publication Information
Molecules and Cells / v.42, no.3, 2019 , pp. 218-227 More about this Journal
Abstract
This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.
Keywords
abdominal aortic aneurysm; apoptosis; extracellular matrix; lncRNA PVT1; vascular smooth muscle cell;
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