Pemafibrate protects the rupture of experimental aortic aneurysm in mice through anti-oxidative stress with induced catalase

Abstract

Abstract Background Abdominal aortic aneurysm (AAA) is a life-threatening disease, while effective and preventive medical treatments remain unestablished. Purpose The aim of this study was to evaluate the effect of selective peroxi- some proliferator-activated receptor alpha (PPARα) modulator pemafibrate on AAA formation in mice. Methods AAA was induced by subcutaneous infusion of angiotensin II (AngII) in apolipoprotein E-deficient mice for 4 weeks. Treatment by pemafibrate or vehicle was started one week before AngII infusion. Oxidative stress was evaluated by dihydroethidium (DHE) staining. Results Prognosis after AngII infusion in pemafibrate-treated mice was significantly better than that in vehicle-treated mice (log-rang test, p=0.035) by reducing the occurrence of fatal AAA rupture. Meanwhile pemafibrate did not significantly reduce maximal diameter of the aorta. Histological findings demonstrated that the expression of collagen in adventitia in pemafibrate-treated mice was significantly greater than that in vehicle-treated mice (p<0.05). Oxidative stress in aorta of pemafibrate-treated mice was significantly reduced comparing to vehicle-treated mice, accompanying by the reduction of mRNA expression of matrix metalloproteinase 2, tumor necrosis factor-α, and interleukin-6 (all p<0.05). Catalase expression in abdominal aortic tissue was increased 1.5-fold in mice treated with pemafibrate than in mice treated with vehicle (p=0.032). In human vascular smooth muscle cells (hVSMC), pemafibrate attenuated AngII-induced oxidative stress (p<0.001), which was canceled by administrating small interfering RNA (siRNA) of PPARα (p<0.001). Furthermore, in hVSMC, pemafibrate increased catalase expression significantly (p<0.001), while this increase was significantly suppressed by knockdown of PPAR-α with siRNA. (p<0.001). Conclusion Pemafibrate reduced the rupture of AAA in this murine model, which is associated with anti-oxidative stress via catalase induction. Funding Acknowledgement Type of funding source: None