Human Apolipoprotein(a) Kringle V Inhibits Ischemia-Induced Retinal Neovascularization via Suppression of Fibronectin-Mediated Angiogenesis
- Yangmi Lim1,
- Dong Hyun Jo2,3,4,
- Jin Hyoung Kim2,
- Jin-Hyung Ahn1,
- Yu Kyeong Hwang1,
- Dong-Ku Kang5,
- Soo-Ik Chang5,
- Young Suk Yu2,3,
- Yeup Yoon1⇓ and
- Jeong Hun Kim2,3,4⇓
- 1Mogam Biotechnology Research Institute, Yongin, Kyonggi-do, Republic of Korea
- 2Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- 3Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea
- 4Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea
- 5Department of Biochemistry, Chungbuk National University, Cheongju, Republic of Korea
- Corresponding authors:
Yeup Yoon, yy{at}greencross.com, and Jeong Hun Kim, steph25{at}snu.ac.kr
-
Y.L. and D.H.J. contributed equally to this work.
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 NH2-terminal kinase. Taken together, our data suggested the possible application of rhLK8 in the treatment of retinal neovascularization by suppression of fibronectin-mediated angiogenesis.
- Received November 2, 2011.
- Accepted February 16, 2012.
- © 2012 by the American Diabetes Association.
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