The inhibitory effect of propylthiouracil on the collagen gene expression in vascular smooth muscle cells

• Main Authors: Su-Hui Yang, 楊舒惠
• Other Authors: Jong-Hwei S. Pang
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/37832815613180315058

碩士 === 長庚大學 === 基礎醫學研究所 === 90 === PTU is used clinically for the treatment of hyperthyroidism. However, overdose might cause hypothyroidism that has been shown to be associated with coronary artery diseases. Pharmacological studies indicate that PTU also exhibits potent antioxidant activity and has the ability to enhance eNOS expression in the vessels. Therefore, the actual effect of PTU on the development of atherosclerosis is still not certain. In our lab, PTU was found to reduce the cholesterol-induced atherosclerosis in rabbit model. The size of a developing atherosclerotic plaque depends on the number of macrophages and SMCs, and extracellular matrix deposition. Collagens constitute up to 60 % of the total plaque proteins. Therefore, this study has investigated the effect of PTU on VSMCs, particularly the synthesis of collagen type I and collagen type III by VSMCs. In vitro data demonstrated that PTU could modulate the phenotype of VSMCs by inhibiting growth, changing morphology and decreasing collagen expression as analyzed by MTT assay, Western blot analysis, immunocytochemistry, Northern blot hybridization, RT-PCR and nuclear run-off. In vivo data revealed that PTU also reduced total collagen proteins in the atherosclerotic plaque of high cholesterol-fed rabbits as analyzed by trichrome stain. In addition, our data also showed that PTU impeded SMCs migration possibly by reason of the decreased collagen expression as examined by transwell filter migration assay. The effect of PTU on modulating functions of VSMCs provides reasonable explaination for the anti-atherosclerotic action of PTU. At last, no effect on VSMCs treated with MMI, another drug for hyperthyroidism, suggested that the effect of PTU on VSMCs is independent of its antithyroid function. Hopefully, through more understandings about the relation between function and chemical structure of PTU, a better drug for preventing atherosclerosis will be developed.