Antirestenosis effect of butein in the neointima formation progression.
The development of restenosis involves migration and hyperproliferation of vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is one of the major factors. Butein modulates inflammatory pathways and affects the proliferation and invasion of the tumor. We investigated the hypothesis that butein might prevent the restenosis process via a similar pathway. Our results demonstrated that butein inhibited PDGF-induced VSMC proliferation and migration as determined by BrdU proliferation and two-dimensional migration scratch assay. Butein also concentration-dependently repressed PDGF-induced phosphorylation of PDGF-receptor β, mitogen-activated protein kinases, phosphoinositide 3-kinase/Akt, and phopholipase Cγ/c-Src in VSMCs. In addition, in vivo results showed that butein attenuated neointima formation in balloon-injured rat carotid arteries. These results indicate that butein may inhibit PDGF-induced VSMC proliferation and migration, resulting in attenuation of neointima formation after percutaneous transluminal coronary angioplasty. Our study demonstrates for the first time that systemic administration of butein is able to reduce neointima formation after vascular injury.
Department of Pharmacology, Tzu Chi University , Hualien, Taiwan.
Yen-Nien
YN
Chen
Tur-Fu
TF
Huang
Chien-Hsin
CH
Chang
Chun-Chieh
CC
Hsu
Kung-Tin
KT
Lin
Shih-Wei
SW
Wang
Hui-Chin
HC
Peng
Ching-Hu
CH
Chung
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D047188:Chalcones; D010982:Platelet-Derived Growth Factor; C040918:butein; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases