Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

Frontiers in Cardiovascular Medicine

article

Naofumi Amioka¹  Toru Miyoshi¹  Tomoko Yonezawa²  Megumi Kondo¹  Satoshi Akagi¹  Masashi Yoshida¹  Yukihiro Saito¹  Kazufumi Nakamura¹  Hiroshi Ito¹ 

[1] Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University;Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

关键词: pemafibrate;    angiotensin II;    abdominal aortic aneurysm;    oxidative stress;    catalase;   

DOI  :  10.3389/fcvm.2022.904215

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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