title: Pyrogallol abates VSMC migration via modulation of Caveolin-1, matrix metalloproteinase and intima hyperplasia in carotid ligation mouse.
abstract: Migration of vascular smooth muscle cells (VSMCs) contributes to intimal hyperplasia and other vascular diseases. Caveolin-1 (Cav-1) has been recognized as a proliferative inhibitor of VSMCs and is likely to be an important regulator of VSMC migration. The underlying mechanism of pyrogallol on the VSMC migration is not fully understood. This study attempted to dissect the role of Cav-1 and matrix metalloproteinase (MMP) in VSMC migration and to investigate the effect of pyrogallol on VSMC mobility during carotid artery ligation mice. The mRNA expression of MMP-3 and MMP-13 was down-regulated in cultured VSMC prepared from Cav-1-deficient (Cav-1 KO) mice whereas MMP-14 expression was up-regulated. Pyrogallol effectively inhibited the migration of Cav-1 KO VSMC by promoting the expression of tissue inhibitors of metalloproteinase (TIMP)-2. Pyrogallol also inhibited the migration of Cav-1 wild type (WT) VSMC, however, by increasing TIMP-1 expression and repressing MMP-2 activity. In a parallel in vivo study, intra-peritoneal (ip) of pyrogallol to carotid artery ligated mice significantly suppressed intima formation in mice carotid artery. Furthermore, the proMMP-9 activity in pyrogallol-treated mice serum significantly increased from Day 0 to Day 2 and decreased from Day 2 to Day 7 in a time-dependent manner. In addition, WT mice treated with pyrogallol had significantly reduced neointima formation, whereas no differences were observed in Cav-1 knock out (KO) mice. These results suggest that pyrogallol not only inhibited VSMC migration but also effectively diminishes the severity of neointima hyperplasia, implying that pyrogallol possesses potential anti-atherogenic effects for the treatment of vascular diseases.
authors: Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan.
authors: Yu-Dong
authors: YD
authors: Ma
authors: Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan.
authors: Varadharajan
authors: V
authors: Thiyagarajan
authors: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei 11221, Taiwan.
authors: May-Jywan
authors: MJ
authors: Tsai
authors: Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan.
authors: Sheng-I
authors: SI
authors: Lue
authors: Department of Food Science & Technology, Tajen University, Ping Tung Hsien, Taiwan.
authors: Yi-Chen
authors: YC
authors: Chia
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Song-Kun
authors: SK
authors: Shyue
authors: Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien 97401, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw.
authors: Ching-Feng
authors: CF
authors: Weng
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D029582:Meliaceae / Q000737:chemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011748:Pyrogallol / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D051242:Caveolin 1; D011748:Pyrogallol; D020782:Matrix Metalloproteinases
keywords: Anti-atherogenic; Caveolin-1; Doxycycline; Matrix metalloproteinase; Pyrogallol; Vascular smooth muscle cells