1. Academic Validation
  2. Silencing of NONO inhibits abdominal aortic aneurysm in apolipoprotein E-knockout mice via collagen deposition and inflammatory inhibition

Silencing of NONO inhibits abdominal aortic aneurysm in apolipoprotein E-knockout mice via collagen deposition and inflammatory inhibition

  • J Cell Mol Med. 2019 Nov;23(11):7449-7461. doi: 10.1111/jcmm.14613.
Xingli Xu 1 Fang Zhang 2 Yue Lu 1 Sufang Yu 3 Wenqian Sun 4 Shangwen Sun 1 Jing Cheng 1 Jing Ma 1 Meng Zhang 1 Cheng Zhang 1 Yun Zhang 1 Kai Zhang 1
Affiliations

Affiliations

  • 1 Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Department of Pharmacy, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
  • 3 Department of Neurology, The Fourth People's Hospital, Liaocheng, China.
  • 4 Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China.
Abstract

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 α1, whereas also decreased the levels of collagen degradation and pro-inflammatory cytokines in AAA. We detected the interface of NONO and NF-κB p65, and found that NONO silencing inhibited both the nuclear translocation and the phosphorylation levels of NF-κB 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-κB.

Keywords

NONO; abdominal aortic aneurysm; collagen deposition; inflammation.

Figures
Products