Angiopoietin-like protein 2 contributes to pathogenesis of diabetic retinopathy

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Abstract

Purpose

Recent studies show that angiopoietin-like protein 2 (Angptl2) contributes to chronic inflammation in diabetes, tumor, rheumatoid arthritis and dermatomyositis, Angptl2 is expressed in endothelial cells, and increased by hypoxia and endoplasmic reticulum stress in HUVEC, and serum level of Angptl2 is increased in diabetes. However, the function of Angptl2 in diabetic retinopathy is still unknown. In this study, we investigate the Angptl2 concentration in vitreous fluid and expression in fibrovascular membrane of PDR patients to evaluate the role of Angptl2 in pathogenesis of diabetic retinopathy.

Methods

We collected vitreous samples at the time of vitreous surgery from 33 PDR and 29 nondiabetic patients. The concentration of Angptl2 in vitreous samples was measured by using the human Angptl2 enzyme-linked immunosorbent assay, and we examined Angptl2 protein expression in fibrovascular membrane from PDR patients by immunohistochemistry using both anti-Angptl2 and anti-CD31 or anti-Mac2 antibody. Next, we examined Angptl2 expression under the hypoxic condition, and ICAM-1 expression induced by Angptl2 in human retinal endothelial cells (HRECs).

Results

The vitreous concentration of Angptl2 significantly increased in patients with PDR compared with controls (P< .001). Double immunofluorescent staining showed that Aangptl2 was expressed in endothelial cells and macrophages in fibrovascular membrane. In vitro study, we found that Angptl2 expression was increased under 2% hypoxic condition in HRECs, and Angptl2 promoted ICAM-1 expression in HREC through the activation of NFkB signaling.

Conclusion

Aangptl2 may play an important role in the pathology of diabetic retinopathy by causing the chronic inflammation in retinal endothelial cells.

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