CARMA3 Deficiency Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysm Development Interacting Between Endoplasmic Reticulum and Mitochondria.
Can J Cardiol
; 39(10): 1449-1462, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37030515
ABSTRACT
BACKGROUND:
Abdominal aortic aneurysm (AAA) is life threatening and associated with vascular walls' chronic inflammation. However, a detailed understanding of the underlying mechanisms is yet to be elucidated. CARMA3 assembles the CARMA3-BCL10-MALT1 (CBM) complex in inflammatory diseases and is proven to mediate angiotensin II (Ang II) response to inflammatory signals by modulating DNA damage-induced cell pyroptosis. In addition, interaction between endoplasmic reticulum (ER) stress and mitochondrial damage is one of the main causes of cell pyroptosis.METHODS:
Male wild type (WT) or CARMA3-/- mice aged 8 to 10 weeks were subcutaneously implanted with osmotic minipumps, delivering saline or Ang II at the rate of 1 µg/kg/min for 1, 2, and 4 weeks.RESULTS:
We discovered that CARMA3 knockout promoted formation of AAA and prominently increased diameter and severity of the mice abdominal aorta infused with Ang II. Moreover, a significant increase in the excretion of inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs) and cell death was found in the aneurysmal aortic wall of CARMA3-/- mice infused with Ang II compared with WT mice. Further studies found that the degree of ER stress and mitochondrial damage in the abdominal aorta of CARMA3-/- mice was more severe than that in WT mice. Mechanistically, CARMA3 deficiency exacerbates the interaction between ER stress and mitochondrial damage by activating the p38MAPK pathway, ultimately contributing to the pyroptosis of vascular smooth muscle cells (VSMCs).CONCLUSIONS:
CARMA3 appears to play a key role in AAA formation and might be a potential target for therapeutic interventions of AAA.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Angiotensina II
/
Aneurisma da Aorta Abdominal
/
Proteínas Adaptadoras de Sinalização CARD
Limite:
Animals
Idioma:
En
Revista:
Can J Cardiol
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China