The role and underlying mechanism of pyrogallol and caveolin-1 on down-regulation of VSMC migration and intima hyperplasia in carotid ligation mouse model

• Main Authors: Yu-Dong Ma, 馬郁東
• Other Authors: Ching-Feng Weng
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/33506614471642656100

碩士 === 國立東華大學 === 生物技術研究所 === 98 === Caveolin-1 (Cav-1) is identified as the major unit forms scaffold structure, regulates several signaling pathway and abundantly expressed in vascular smooth muscle cell (VSMC). VSMC migration contributes to intimal hyperplasia, which is involved in several vascular diseases including atherosclerosis. Previous study demonstrated that Cav-1-deficient VSMC showed an abnormal increase in proliferation and migration rate as compared with wild-type. The mechanism of Cav-1 in VSMC proliferation is already demonstrated, but the role of Cav-1 in VSMC migration has not been certain. In addition, Pyrogallol, a polyphenol compound, plays an antioxidant character and reduces the risk of cardiovascular disease. This study attempted to dissect the role of Cav-1 in VSMC migration and investigate effect of pyrogallol on VSMC mobility and carotid artery ligation to mimic a neointimal hyperplasia phenotype. The data showed that Cav-1 deficient VSMC down-regulated the mRNA expression of MMP-3, MMP-13 and cox-2 whereas up-regulated of MMP-14 expression. Moreover, the AFM picture also showed that Cav-1 deficient VSMC had less lamellipodia and higher filopodia than wild-type VSMC. Additionally, Pyrogallol could significantly inhibit VSMC migration in the presence and absence of Cav-1 via two different pathways. Pyrogallol inhibited WT VSMC migration by repressing MMP-2 activity and increasing TIMP-1 expression. In contrast, without Cav-1 in VSMC, pyrogallol inhibits its migration via promoting the TIMP-2 expression and down-regulating MMP-1 expression. In vivo study, pyrogallol also could significantly inhibit the intima formation at third week after mouse carotid ligation. At the early stage of carotid ligation in mice, the proMMP-9 was significantly increased from Day 0 to Day 2 and decreased from Day 2 to Day 7 at a time-dependent manner from zymography of serum. Furthermore, MMP-9 activity was elevated from Day 2 to Day 7. However there was no significant difference in both MMP-2 and MMP-9 activity after treated with pyrogallol and doxycycline for 8 times, respectively. The present study suggests that pyrogallol could prevent the severity of neointima hyperplasia via a ROS scavenger in mouse carotid ligation model and has potential anti-atherogenic effects in the treatment of vascular diseases.