Human Apolipoprotein(a) Kringle V Inhibits Ischemia-Induced Retinal Neovascularization via Suppression of Fibronectin-Mediated Angiogenesis

Mogam Biotechnology Research Institute, Yongin, Kyonggi-do, Republic of Korea.
Diabetes (Impact Factor: 8.1). 03/2012; 61(6):1599-608. DOI: 10.2337/db11-1541
Source: PubMed


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.

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    • "However, the role of apo(a)/Lp(a) in this context remains highly controversial, as reflected by a number of conflicting reports in the literature. For example, findings range from a positive effect using Lp(a) [18], to no effect using full-length recombinant apo(a) [19] or an apo(a) fragment [20], to an inhibitory effect using either full-length recombinant apo(a) [20], [21] or different fragments of apo(a) [21]–[24]. Fundamental differences exist between these studies, including sources of purified apo(a)/Lp(a) (from bacterial versus mammalian recombinant expression systems, for example) and choice of models used to identify and quantify angiogenesis. Importantly, the bacterially-expressed apo(a) lacks glycosylation modification which may influence the variable results obtained in some models of angiogenesis. "
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