Angiopoietin-like protein 8 deficiency attenuates thoracic aortic aneurysm/dissection development in β-aminopropionitrile monofumarate-induced model mice

Dec 9, 2022Biochimica et biophysica acta. Molecular basis of disease

Lack of Angiopoietin-like Protein 8 reduces the development of aortic bulges and tears in a mouse model

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Abstract

ANGPTL8 knockout in mice reduced the TAAD rupture rate to 0%.

  • Increased levels of ANGPTL8 were observed in the aortic wall and vascular smooth muscle cells of mice with TAAD induced by BAPN.
  • Knockout of ANGPTL8 resulted in a significant decrease in the rupture rate of TAAD.
  • Decreased levels of proinflammatory cytokines, matrix metalloproteinase 9 (MMP9), and endoplasmic reticulum stress proteins were noted in the aorta wall of ANGPTL8 knockout mice.
  • Knockdown of ANGPTL8 in vascular smooth muscle cells led to reduced MMP9 and endoplasmic reticulum stress protein levels.
  • Overexpression of ANGPTL8 increased levels of endoplasmic reticulum stress proteins and MMPs in vascular smooth muscle cells.
  • Inhibition of the PERK pathway significantly diminished the effects of ANGPTL8 in vascular smooth muscle cells.

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