Efficacy of peroxisome proliferative activated receptor (PPAR)-α ligands, fenofibrate, on intimal hyperplasia and constrictive remodeling after coronary angioplasty in porcine models

Abstract 

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)-α 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 (6.28mm² versus 5.15mm²), vessel area (7.34mm² versus 6.69mm²) 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-α inhibited constrictive remodeling and neointimal hyperplasia after angioplasty through inhibition of inflammation and adventitial neovascularization.

Keywords: Constrictive remodeling, Adventitial angiogenesis, Inflammation, Peroxisome proliferative activated receptors (PPAR)-α, Intimal hyperplasia, Fenofibrate, Balloon angioplasty, Restenosis, Porcine coronary artery