Kim Jang-Seong, Yu Hyun-Kyung, Ahn Jin-Hyung, Lee Ho-Jeong, Hong Soon-Won, Jung Kyung-Hwan, Chang Soo-Ik, Hong Yong-Kil, Joe Young-Ae, Byun Si-Myung, Lee Suk-Keun, Chung Soo-Il, Yoon Yeup
Mogam Biotechnology Research Institute, Yongin-city, Kyonggi-do 449-910, Republic of Korea.
Biochem Biophys Res Commun. 2004 Jan 16;313(3):534-40. doi: 10.1016/j.bbrc.2003.11.148.
Apolipoprotein(a) [apo(a)] contains the largest numbers of kringle domains identified to date. Of these, apo(a) kringle V shows significant sequence homology with plasminogen kringle 5, which is reported to be a potent angiogenesis inhibitor. To determine the effects of apo(a) kringle V on angiogenesis, it was expressed as a soluble protein (termed rhLK8) in Pichia pastoris and its in vitro and in vivo anti-angiogenic properties were examined. rhLK8 inhibited the migration of human umbilical vein endothelial cells in vitro in a dose-dependent manner. This function was associated with the down-regulation of the activation of focal adhesion kinase and the inhibition of the consequent formation of actin stress fibers/focal adhesions. rhLK8 also inhibited new capillary formation in vivo, as assessed by the chick chorioallantoic membrane assay and the Matrigel plug assay. These results indicate that rhLK8 may be an effective angiogenesis inhibitor both in vitro and in vivo.
载脂蛋白(a)[apo(a)]含有迄今为止已鉴定出的数量最多的kringle结构域。其中，apo(a)kringle V与纤溶酶原kringle 5具有显著的序列同源性，据报道纤溶酶原kringle 5是一种有效的血管生成抑制剂。为了确定apo(a)kringle V对血管生成的影响，它在毕赤酵母中作为可溶性蛋白（称为rhLK8）表达，并检测其体外和体内抗血管生成特性。rhLK8在体外以剂量依赖的方式抑制人脐静脉内皮细胞的迁移。该功能与粘着斑激酶激活的下调以及随后肌动蛋白应力纤维/粘着斑形成的抑制有关。通过鸡胚绒毛尿囊膜试验和基质胶栓试验评估，rhLK8在体内也抑制新毛细血管的形成。这些结果表明，rhLK8在体外和体内可能都是一种有效的血管生成抑制剂。
