Upregulation of peroxisome proliferator-activated receptor-gamma and NADPH oxidases are involved in restenosis after balloon injury.
Restenosis is a major complication of percutaneous transluminal coronary angioplasty (PTCA) and is characterized by increased superoxide formation and accumulation of smooth muscle cells (SMCs). The mechanisms through which peroxisome proliferator-activated receptor-gamma (PPAR-gamma) modulates the pathological process are incompletely defined. In this study, balloon injury of porcine coronary arteries in vivo and cell scraping model in vitro were used to elucidate the pathway via this molecule. PPAR-gamma and NADPH oxidase expression significantly increased both in neointimal hyperplasia after balloon injury or in the cultured SMCs after scraping injury. In vitro, PPAR-gamma agonist 15-deoxy-Delta(12,14)-prostagladlin J(2) (15d-PGJ2) decreased cell-scraping-induced superoxide generation through suppression of NADPH oxidase activity via down-regulation of p22(phox) and gp91(phox). Furthermore, 15d-PGJ2 could suppress scraping-stimulated proliferation of SMCs. These data demonstrate that upregulation of PPAR-gamma and NADPH oxidases are involved in restenosis and activation of PPAR-gamma can inhibit the NADPH oxidase-dependent superoxide generation in SMCs after injury. These findings will provide a new potential drug target for restenosis after balloon injury.
Qin
Hai-Dong
HD
Department of Emergency, Nanjing Medical University, Affiliated Nanjing First Hospital, Jiangsu, China.
Huang
Dan
D
Weng
Xiao-Dan
XD
Xu
Feng
F
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D023903:Coronary Restenosis / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D034421:Sus scrofa; D015854:Up-Regulation / Q000187:drug effects
C477819:15-deoxyprostaglandin J2; D047495:PPAR gamma; D021122:Protein Subunits; D013481:Superoxides; D019255:NADPH Oxidases; D015230:Prostaglandin D2