Overexpressed DDX3x promotes abdominal aortic aneurysm formation and activates AKT in ApoE knockout mice

Biochem Biophys Res Commun. 2022 Dec 17:634:138-144. doi: 10.1016/j.bbrc.2022.09.077. Epub 2022 Sep 24.

Abstract

In recent years, abdominal aortic aneurysm (AAA) lesions have become one of the important diseases that threaten public health. Related studies have confirmed that the occurrence of abdominal aortic aneurysms is related to inflammatory stress, cell apoptosis, and elastic fiber degradation. DDX3x is thought to interact with inflammasomes such as NLRP3 to aggravate the process of the inflammatory response, but its role in the occurrence of AAA remains unclear. Since DDX3x is indispensable in animal embryonic growth, we used an adeno-associated virus to construct gene-overexpressing mice to induce aneurysm development through AngII infusion. The results indicated that the incidence of aneurysms, inflammatory cell infiltration, vascular smooth muscle cell transformation, and oxidative stress levels were significantly increased under the condition of DDX3x overexpression. At the signaling level, activation of the AKT pathway exacerbates aneurysm formation. Taken together, we believe that DDX3x plays a key role in the development of aneurysms and may be a new target for the treatment of aneurysm progression.

Keywords: AKT; Abdominal aortic aneurysm; DDX3x; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal* / pathology
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Knockout, ApoE
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Angiotensin II
  • Ddx3x protein, mouse
  • DEAD-box RNA Helicases