Human apolipoprotein(a) kringle V inhibits angiogenesis in vitro and in vivo by interfering with the activation of focal adhesion kinases.
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.
Kim
Jang-Seong
JS
Mogam Biotechnology Research Institute, Yongin-city, Kyonggi-do 449-910, Republic of Korea.
Yu
Hyun-Kyung
HK
Ahn
Jin-Hyung
JH
Lee
Ho-Jeong
HJ
Hong
Soon-Won
SW
Jung
Kyung-Hwan
KH
Chang
Soo-Ik
SI
Hong
Yong-Kil
YK
Joe
Young-Ae
YA
Byun
Si-Myung
SM
Lee
Suk-Keun
SK
Chung
Soo-Il
SI
Yoon
Yeup
Y
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D053241:Apoprotein(a); D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005822:Genetic Vectors; D006801:Humans; D018082:Kringles; D007797:Laminin / Q000494:pharmacology; D017270:Lipoprotein(a) / Q000737:chemistry*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014945:Wound Healing
D000199:Actins; D001053:Apolipoproteins; D018076:DNA, Complementary; D004338:Drug Combinations; D007797:Laminin; D017270:Lipoprotein(a); D011509:Proteoglycans; D011994:Recombinant Proteins; C059485:matrigel; D014443:Tyrosine; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D053241:Apoprotein(a)