Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

Naofumi Amioka, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Satoshi Akagi, Masashi Yoshida, Yukihiro Saito, Kazufumi Nakamura, Hiroshi Itoh

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE/ mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

Original languageEnglish
Article number904215
JournalFrontiers in Cardiovascular Medicine
Volume9
DOIs
Publication statusPublished - Jun 30 2022

Keywords

  • abdominal aortic aneurysm
  • angiotensin II
  • catalase
  • oxidative stress
  • pemafibrate

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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