title: Human apolipoprotein(a) kringle V inhibits angiogenesis in vitro and in vivo by interfering with the activation of focal adhesion kinases.
abstract: 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.
authors.affiliation: Mogam Biotechnology Research Institute, Yongin-city, Kyonggi-do 449-910, Republic of Korea.
authors.forename: Jang-Seong
authors.initials: JS
authors.lastname: Kim
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Yu
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Ahn
authors.forename: Ho-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Soon-Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Jung
authors.forename: Soo-Ik
authors.initials: SI
authors.lastname: Chang
authors.forename: Yong-Kil
authors.initials: YK
authors.lastname: Hong
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Joe
authors.forename: Si-Myung
authors.initials: SM
authors.lastname: Byun
authors.forename: Suk-Keun
authors.initials: SK
authors.lastname: Lee
authors.forename: Soo-Il
authors.initials: SI
authors.lastname: Chung
authors.forename: Yeup
authors.initials: Y
authors.lastname: Yoon
mesh_terms: 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
chemical_list: 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)