标题：Silencing of NONO inhibits abdominal aortic aneurysm in apolipoprotein E-knockout mice via collagen deposition and inflammatory inhibition
作者：Xu, Xingli; Zhang, Fang; Lu, Yue; Yu, Sufang; Sun, Wenqian; Sun, Shangwen; Cheng, Jing; Ma, Jing; Zhang, Meng; Zhang, Cheng; Zhang 更多 作者机构：[Xu, Xingli; Lu, Yue; Sun, Shangwen; Cheng, Jing; Ma, Jing; Zhang, Meng; Zhang, Cheng; Zhang, Yun; Zhang, Kai] Shandong Univ, Dept Cardiol, Key Lab Ca 更多
通讯作者地址：[Zhang, K]Shandong Univ, Qilu Hosp, 107 Wen Hua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
关键词：abdominal aortic aneurysm; collagen deposition; inflammation; NONO
摘要：The role of Non-POU-domain-containing octamer-binding protein (NONO) in the formation and development of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) in apolipoprotein E-knockout (ApoE(-/-)) mice is still unknown. In Part I, the protein level of NONO was suggestively greater in the AAA tissues compare to that in the normal abdominal aortas. In Part II, 20 ApoE(-/-) male mice were used to examine the transfection efficiency of lentivirus by detecting GFP fluorescence. In Part III, mice were arbitrarily separated into two groups: one was the control group without Ang II infusion, and another was the Ang II group. Mice treated with Ang II were further randomly divided into three groups to receive the same volume of physiological saline (NT group), sh-negative control lentivirus (sh-NC group) and si-NONO lentivirus (sh-NONO group). NONO silencing suggestively reduced the occurrence of AAA and abdominal aortic diameter. Compare to the NT group, NONO silencing markedly augmented the content of collagen and vascular smooth muscle cells but reduced macrophage infiltration in AAA. In addition, knockdown of NONO also increased the expression of prolyl-4-hydroxylase alpha 1, whereas also decreased the levels of collagen degradation and pro-inflammatory cytokines in AAA. We detected the interface of NONO and NF-kappa B p65, and found that NONO silencing inhibited both the nuclear translocation and the phosphorylation levels of NF-kappa B p65. Silencing of NONO prevented Ang II-influenced AAA in ApoE(-/-) mice through increasing collagen deposition and inhibiting inflammation. The mechanism may be that silencing of NONO decreases the nuclear translocation and phosphorylation of NF-kappa B.