title: Human apolipoprotein(a) kringle V inhibits ischemia-induced retinal neovascularization via suppression of fibronectin-mediated angiogenesis.
abstract: Retinal neovascularization is observed in progression of diabetic retinopathy. New vessels grow into the vitreous cavity in proliferative diabetic retinopathy, resulting in traction retinal detachment and vitreous hemorrhage. To overcome the catastrophic visual loss due to these complications, efforts have been focused on the treatment of retinal neovascularization. In this study, we demonstrated the inhibitory effect of recombinant human apolipoprotein(a) kringle V (rhLK8) in an animal model of ischemia-induced retinal neovascularization. rhLK8 induced no definite toxicity on endothelial cells and retinal tissues at the therapeutic dosage. Interestingly, rhLK8 showed antiangiogenic effect, particularly on fibronectin-mediated migration of endothelial cells. Further experiments demonstrated high binding affinity of rhLK8 to α3β1 integrin, and suppression of it might be the mechanism of antiangiogenic effect of rhLK8. Furthermore, rhLK8 inhibited phosphorylation of focal adhesion kinase, resulting in suppression of activation of consequent p130CAS-Jun NH(2)-terminal kinase. Taken together, our data suggested the possible application of rhLK8 in the treatment of retinal neovascularization by suppression of fibronectin-mediated angiogenesis.
authors.affiliation: Mogam Biotechnology Research Institute, Yongin, Kyonggi-do, Republic of Korea.
authors.forename: Yangmi
authors.initials: Y
authors.lastname: Lim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Ahn
authors.forename: Yu Kyeong
authors.initials: YK
authors.lastname: Hwang
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kang
authors.forename: Soo-Ik
authors.initials: SI
authors.lastname: Chang
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Yeup
authors.initials: Y
authors.lastname: Yoon
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000494:pharmacology / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001054:Apolipoproteins A; D005353:Fibronectins; D051416:Focal Adhesion Protein-Tyrosine Kinases