串珠素表达下调参与缺氧对大鼠心肌微血管内皮细胞增殖的抑制作用.pdfVIP

Acta Physiologica Sinica , April 25, 2007, 59 (2): 221-226 221 Research Paper Down-regulation of perlecan expression contributes to the inhibition of rat cardiac microvascular endothelial cell proliferation induced by hypoxia * LI Yu-Zhen, LIU Xiu-Hua , CAI Li-Rong Department of Pathophysiology, Institute of Basic Medical Science, PLA General Hospital, Beijing 100853, China Abstract: Exposure of endothelial cells (ECs) to hypoxia leads to a decrease in EC proliferation. However, the mechanism by which hypoxia inhibits EC proliferation is unclear. Perlecan has been reported to play an important role in regulating EC proliferation. We hypothesized that perlecan was involved in the hypoxia-induced inhibition of EC proliferation. To test this hypothesis, rat cardiac microvascular ECs were cultured under normoxic or hypoxic conditions for 12 h and harvested for determination of perlecan mRNA expression using real-time reverse transcription-polymerase chain reaction (RT-PCR). The results showed that exposure of ECs to hypoxia for 12 h induced a decrease in perlecan mRNA expression (61.72%, P0.05). Concomitantly, the down-regulation of endo- genous perlecan induced by hypoxia or the neutralization of endogenous perlecan with anti-perlecan antibody significantly inhibited EC proliferation and responsiveness to basic fibroblast growth factor (bFGF), and decreased focal adhesion kinase (FAK) expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. These data indicate that down-regulation of perlecan expression contributes to hypoxia-induced inhibition of rat cardiac microvascular EC proliferation by suppressing FAK-mediated and ERK1/2- dependent growth signals. Key words: hypoxia; endothelial cell; cell proliferation; perlecan 串珠素表达下调参与低氧对大鼠心肌微血管内皮细胞增殖的抑制作用 * 李玉珍，刘秀华 ，蔡莉蓉 北京解放军总医院基础医学所病理生理研究室，北京 100853 摘 要：低氧可以抑制内皮细胞增殖，但