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促血管生成和抗血管生成的血管内皮生长因子(VEGF)及其受体状态与糖尿病视网膜病变严重程度的关系

Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy.

作者信息

Paine Suman K, Mondal Lakshmi K, Borah Prasanta K, Bhattacharya Chandra K, Mahanta Jagadish

机构信息

Regional Medical Research Centre-NE Region (Indian Council of Medical Research), Assam, India.

Regional Institute of Ophthalmology, Kolkata, India.

出版信息

Mol Vis. 2017 Jun 22;23:356-363. eCollection 2017.

Abstract

PURPOSE

Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGFa) and antiangiogenic (VEGFb) VEGF isoforms and its soluble receptors for severity of DR.

METHODS

The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGFa (proangiogenic), VEGFb (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA).

RESULTS

An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGFa and a decrease in the level of VEGFb, was observed with the severity of the disease. Increased differences between VEGFa and VEGFb i.e. VEGFa-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001).

CONCLUSIONS

The increased difference or imbalance between the pro- (VEGFa) and antiangiogenic (VEGFb) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform.

摘要

目的

高血糖患者血管内皮生长因子(VEGF)亚型的促血管生成和抗血管生成稳态改变似乎至关重要,但至少在糖尿病视网膜病变(DR)的定量方面尚未得到充分研究。因此,在本研究中,我们旨在评估促血管生成(VEGFa)和抗血管生成(VEGFb)VEGF亚型及其可溶性受体之间的差异与DR严重程度的关系。

方法

该研究纳入了来自加尔各答地区眼科研究所的123名参与者(糖尿病视网膜病变:81例,糖尿病对照:20例,非糖尿病对照:22例)。采用酶联免疫吸附测定(ELISA)法测定血浆中VEGFa(促血管生成)、VEGFb(抗血管生成)、VEGF受体1(VEGFR1)、VEGFR2和VEGFR3的蛋白水平。

结果

随着疾病严重程度的增加,观察到VEGF稳态失衡,即VEGFa水平在统计学上显著升高(p<0.0001),而VEGFb水平降低。VEGFa和VEGFb之间的差异增加,即VEGFa-b随着疾病严重程度的增加在统计学上显著升高(p<0.0001),伴有增殖性DR的弥漫性糖尿病黄斑水肿(DME)患者的失衡最为严重。VEGFR2浓度的血浆可溶性形式随着疾病严重程度的增加在统计学上持续显著升高(p<0.0001)。

结论

VEGF亚型的促血管生成(VEGFa)和抗血管生成(VEGFb)稳态之间的差异增加或失衡,似乎对DR的不良预后至关重要,并且与任一VEGF亚型相比可能是更好的解释性标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6602/5482372/08a3720e9f54/mv-v23-356-f1.jpg

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