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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2300862


Alamandine inhibits pathological retinal neovascularization by targeting MrgD-mediated HIF-1α/VEGFA pathway


Author(s):  Kun ZHAO, Yaping JIANG, Wen HUANG, Yukang MAO, Yihui CHEN, Peng LI, Chuanxi YANG

Affiliation(s):  Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China; more

Corresponding email(s):   lipeng198610@163.com, 2205515@tongji.edu.cn

Key Words:  Alamandine, Pathological neovascularization, Retinopathy of prematurity (ROP), Oxygen-induced retinopathy (OIR), MrgD, VEGFA


Kun ZHAO, Yaping JIANG, Wen HUANG, Yukang MAO, Yihui CHEN, Peng LI, Chuanxi YANG. Alamandine inhibits pathological retinal neovascularization by targeting MrgD-mediated HIF-1α/VEGFA pathway[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .

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author="Kun ZHAO, Yaping JIANG, Wen HUANG, Yukang MAO, Yihui CHEN, Peng LI, Chuanxi YANG",
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publisher="Zhejiang University Press & Springer",
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%T Alamandine inhibits pathological retinal neovascularization by targeting MrgD-mediated HIF-1α/VEGFA pathway
%A Kun ZHAO
%A Yaping JIANG
%A Wen HUANG
%A Yukang MAO
%A Yihui CHEN
%A Peng LI
%A Chuanxi YANG
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T1 - Alamandine inhibits pathological retinal neovascularization by targeting MrgD-mediated HIF-1α/VEGFA pathway
A1 - Kun ZHAO
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A1 - Yihui CHEN
A1 - Peng LI
A1 - Chuanxi YANG
J0 - Journal of Zhejiang University Science B
VL - -1
IS - -1
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Y1 - 1998
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2300862


Abstract: 
retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system, on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μM/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/ml) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. The LC-MS/MS analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice when compared to the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch-wound healing, and tube formation of HRMECs primarily by inhibiting the HIF-1α/VEGF pathway. Further, coincubation with D-Pro7 (Mas-related G protein-coupled receptor D (mrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the mrgD-mediated HIF-1α/VEGFA pathway, providing a potential therapeutic agent for OIR prevention and treatment.

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