Efficacy of peroxisome proliferative activated receptor (PPAR)-alpha ligands, fenofibrate, on intimal hyperplasia and constrictive remodeling after coronary angioplasty in porcine models.
Constrictive remodeling and intimal hyperplasia play a prominent role in restenosis after angioplasty. It has been reported that the severity of constrictive remodeling and intimal hyperplasia correlate with adventitial angiogenesis and inflammation. Experimental evidence indicates that inflammation participates in angiogenesis, and therefore inhibition of inflammation may impair neovascularization. We tested whether fenofibrate, peroxisome proliferative activated receptors (PPAR)-alpha specific ligand, inhibits the early inflammation, adventitial angiogenesis, constrictive remodeling and intimal hyperplasia after angioplasty using porcine coronary arteries. Fenofibrate was tested in vivo, in 30 coronary arteries of 10 pigs (1g/day, orally) and was compared to placebo. Quantitative intravascular ultrasound and histopathologic assessment showed that fenofibrate increased lumen (6.28 mm(2) versus 5.15 mm(2)), vessel area (7.34 mm(2) versus 6.69 mm(2)) and inhibited constrictive remodeling. Inflammatory cell infiltration was evaluated with scanning electron microscopy 3 days after angioplasty and was significantly decreased in the treated vessels compared to control. Adventitial angiogenesis 3 days after angioplasty was significantly reduced in the injured vessels derived from the fenofibrate treated group compared to placebo. In conclusion, pharmacological activation of PPAR-alpha inhibited constrictive remodeling and neointimal hyperplasia after angioplasty through inhibition of inflammation and adventitial neovascularization.
Kasai
Takatoshi
T
Department of Cardiology, Juntendo University, School of Medicine, Tokyo, Japan.
Miyauchi
Katsumi
K
Yokoyama
Takayuki
T
Aihara
Kouichiro
K
Daida
Hiroyuki
H
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery*; D011345:Fenofibrate / Q000378:metabolism / Q000494:pharmacology*; D006965:Hyperplasia / Q000188:drug therapy* / Q000209:etiology; D007150:Immunohistochemistry; D008024:Ligands; D009389:Neovascularization, Pathologic / Q000473:pathology; D047493:PPAR alpha / Q000378:metabolism; D034421:Sus scrofa; D014463:Ultrasonography
D008024:Ligands; D047493:PPAR alpha; D011345:Fenofibrate