Pemafibrate, a PPAR alpha agonist, attenuates neointima formation after vascular injury in mice fed normal chow and a high-fat diet

Heliyon
Tsuyoshi HorikawaTakashi Nomiyama

Abstract

Recently, the prevention of cardiovascular events has become one of the most important aims of diabetes care. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported to have vascular protective effects. Here, we examined whether pemafibrate, a selective PPAR alpha agonist, attenuated neointima formation after vascular injury and vascular smooth muscle cell (VSMC) proliferation. We performed endothelial denudation injury in mice treated with a high-fat diet (HFD) or normal chow. Orally administered pemafibrate significantly attenuated neointima formation after vascular injury in HFD and normal chow mice. Interestingly, pemafibrate increased the serum fibroblast growth factor 21 concentration and decreased serum insulin concentrations in HFD mice. In addition, body weight was slightly but significantly decreased by pemafibrate in HFD mice. Pemafibrate, but not bezafibrate, attenuated VSMC proliferation in vitro. The knockdown of PPAR alpha abolished the anti-VSMC proliferation effect of pemafibrate. BrdU assay results revealed that pemafibrate dose-dependently inhibited DNA synthesis in VSMCs. Flow cytometry analysis demonstrated that G1-to-S phase cell cycle transition was significantly inhibited by pemafib...Continue Reading

References

Dec 20, 2008·Journal of the American College of Cardiology·Anne HiukkaMarja-Riitta Taskinen
Sep 3, 2010·Current Vascular Pharmacology·Danna M Breen, Adria Giacca
Nov 3, 2010·European Journal of Pharmacology·Jung-Jin LeeYeo-Pyo Yun
Jan 11, 2011·Biochemical and Biophysical Research Communications·Hiromasa GotoHirotaka Watada
Nov 20, 2014·Cardiovascular Diabetology·Yuichi TerawakiToshihiko Yanase
Jan 7, 2018·Biochemical and Biophysical Research Communications·Yun ZhaoXin Jin
Jul 3, 2018·Journal of Atherosclerosis and Thrombosis·Hiroyuki TakahashiToshihiko Yanase
Jul 26, 2018·International Journal of Molecular Sciences·Masaya ArakiHitoshi Shimano
Sep 2, 2018·Cellular Signalling·Agne FrismantieneTherese J Resink
Aug 24, 2019·Progress in Cardiovascular Diseases·Tushar Acharya, Prakash Deedwania
Nov 27, 2019·International Journal of Molecular Sciences·Yusuke SasakiTatsuhiko Kodama
Nov 28, 2019·International Journal of Molecular Sciences·Yohei TomitaToshihide Kurihara

❮ Previous
Next ❯

Methods Mentioned

BETA
confocal microscopy
ELISA
flow cytometry
PCR

Software Mentioned

GraphPad Prism
GraphPad
FlowJo

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis