Research progress in the role and mechanism of angiopoietin-like protein in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Tian Ye ¹ ,  Zhang Guoheng ^1,2 , Dou Guorui ¹

1. Department of Ophthalmology, Eye Institute of PLA, Xijing Hospital, The Air Force Medical University, Xi'an 710032, China;
2. Department of Ophthalmology, 942 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Yinchuan 750000, China;

Corresponding author：

Zhang Guoheng, Email: zhangguoheng2316@163.com

Keywords：

Angiopoietin-like protein; Diabetic retinopathy; Molecular mechanism; Targeted drug; Review

DOI：

10.3760/cma.j.cn511434-20240227-00085

Video：

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Abstract Full text Figures/Tables Video References Cited by

Angiopoietin-like protein (ANGPTL), a group of secreted glycoproteins, is widely expressed in vivo and is involved in many pathophysiological processes such as glycolipid metabolism, stem cell growth, local inflammation, vascular leakage and angiogenesis. Many kinds of ANGPTL are closely related to the occurrence and development of diabetic retinopathy (DR), especially ANGPTL4, which has gradually become a new hotspot in the field of DR Research. ANGPTL is involved in glucose metabolism and lipid metabolism, promotes increased vascular permeability, pathological angiogenesis, and participates in intraocular inflammation. ANGPTL is a promising molecular target. It can not only be used as a biomarker to predict the occurrence and progression of DR, but also provide new ideas for the treatment of DR by making antibody drugs to interfere with this molecule.

Citation： Tian Ye, Zhang Guoheng, Dou Guorui. Research progress in the role and mechanism of angiopoietin-like protein in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2024, 40(7): 569-574. doi: 10.3760/cma.j.cn511434-20240227-00085 Copy

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2. Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045 systematic review and meta-analysis[J]. Ophthalmology, 2021, 128(11): 1580-1591. DOI: 10.1016/j.ophtha.2021.04.027.
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4. Santulli G. Angiopoietin-like proteins: a comprehensive look[J/OL]. Front Endocrinol (Lausanne), 2014, 5: 4[2014-01-23]. https://pubmed.ncbi.nlm.nih.gov/24478758/. DOI: 10.3389/fendo.2014.00004.
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6. Lu Q, Zou W, Chen B, et al. ANGPTL-4 correlates with vascular endothelial growth factor in patients with proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2016, 254(7): 1281-1288. DOI: 10.1007/s00417-015-3187-8.
7. Kwon SH, Shin JP, Kim IT, et al. Aqueous levels of angiopoietin-like 4 and semaphorin 3E correlate with nonperfusion area and macular volume in diabetic retinopathy[J]. Ophthalmology, 2015, 122(5): 968-975. DOI: 10.1016/j.ophtha.2015.01.007.
8. Yan J, Li WJ, Qin YZ, et al. Aqueous angiopoietin-like levels correlate with optical coherence tomography angiography metrics in diabetic macular edema[J]. Int J Ophthalmol, 2021, 14(12): 1888-1894. DOI: 10.18240/ijo.2021.12.12.
9. Xu Q, Gong C, Qiao L, et al. Aqueous level of ANGPTL4 correlates with the OCTA metrics of diabetic macular edema in NPDR[J/OL]. J Diabetes Res, 2022, 2022: 8435603[2022-01-19]. https://pubmed.ncbi.nlm.nih.gov/35097131/. DOI: 10.1155/2022/8435603.
10. 滕月, 曾筱婷, 罗英子, 等. 糖尿病视网膜病变房水中细胞因子的检测及其临床意义[J]. 中华实验眼科杂志, 2023, 41(1): 55-62. DOI: 10.3760/cma.j.cn115989-20201203-00817.Teng Y, Zeng XT, Luo YZ, et al. Detection of aqueous humor cytokines in diabetic retinopathy and its clinical significance[J]. Chin J Pract Ophthalmol, 2023, 41(1): 55-62. DOI: 10.3760/cma.j.cn115989-20201203-00817.
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12. Keles A, Sonmez K, Erol YO, et al. Vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1 alpha, and angiopoietin-like protein 2 in patients with active proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2021, 259(1): 53-60. DOI: 10.1007/s00417-020-04889-0.
13. Wang YY, Zhang D, Jiang ZY, et al. Positive association between betatrophin and diabetic retinopathy risk in type 2 diabetes patients[J]. Horm Metab Res, 2016, 48(3): 169-173. DOI: 10.1055/s-0035-1550009.
14. Fang C, Huang Y, Guo H, et al. Lipasin, a biomarker of diabetic retinopathy[J]. Diabetes Res Clin Pract, 2016, 115: 96-98. DOI: 10.1016/j.diabres.2016.01.029.
15. Pehlivan V, Gursu MF, Citak O, et al. Evaluation of serum ANGPTL8/betatrophin and cartonectin/CTRP3 l levels in diabetic and non-diabetic retinopathy[J]. J Coll Physicians Surg Pak, 2023, 33(1): 66-72. DOI: 10.29271/jcpsp.2023.01.66.
16. Lu Q, Lu L, Chen W, et al. Expression of angiopoietin-like protein 8 correlates with VEGF in patients with proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2017, 255(8): 1515-1523. DOI: 10.1007/s00417-017-3676-z.
17. Güngör Kobat S, Gül FC, Çelik F, et al. Plasma and aqueous levels of subfatin, preptin and betatrophin in patients with diabetic retinopathy[J]. BMC Ophthalmol, 2023, 23(1): 312. DOI: 10.1186/s12886-023-03075-0.
18. 中华医学会眼科学分会眼底病学组, 中国医师协会眼科医师分会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2022年)[J]. 中华眼底病杂志, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022)[J]. Chin J Ocul Fundus Dis, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.
19. Feng S, Yu H, Yu Y, et al. Levels of inflammatory cytokines IL-1β, IL-6, IL-8, IL-17A, and TNF-α in aqueous humour of patients with diabetic retinopathy[J/OL]. J Diabetes Res, 2018, 2018: 8546423[2018-04-04]. https://pubmed.ncbi.nlm.nih.gov/29850610/. DOI: 10.1155/2018/8546423.
20. Mizuno S, Seishima R, Yamasaki J, et al. Angiopoietin-like 4 promotes glucose metabolism by regulating glucose transporter expression in colorectal cancer[J]. J Cancer Res Clin Oncol, 2022, 148(6): 1351-1361. DOI: 10.1007/s00432-022-03960-z.
21. Zhao Z, Deng X, Jia J, et al. Angiopoietin-like protein 8 (betatrophin) inhibits hepatic gluconeogenesis through PI3K/Akt signaling pathway in diabetic mice[J/OL]. Metabolism, 2022, 126: 154921[2022-10-27]. https://pubmed.ncbi.nlm.nih.gov/34715116/. DOI: 10.1016/j.metabol.2021.154921.
22. Wu Z, Liu J, Chen G, et al. CD146 is a novel ANGPTL2 receptor that promotes obesity by manipulating lipid metabolism and energy expenditure[J/OL]. Adv Sci (Weinh), 2021, 8(6): 2004032[2021-01-27]. https://pubmed.ncbi.nlm.nih.gov/33747748/. DOI: 10.1002/advs.202004032.
23. Shimamura M, Matsuda M, Yasumo H, et al. Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase[J]. Arterioscler Thromb Vasc Biol, 2007, 27(2): 366-372. DOI: 10.1161/01.Atv.0000252827.51626.89.
24. Leth-Espensen KZ, Kristensen KK, Kumari A, et al. The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding[J/OL]. Proc Natl Acad Sci USA, 2021, 118(12): e2026650118[2021-03-23]. https://pubmed.ncbi.nlm.nih.gov/33723082/. DOI: 10.1073/pnas.2026650118.
25. Yau MH, Wang Y, Lam KS L, et al. A highly conserved motif within the NH2-terminal coiled-coil domain of angiopoietin-like protein 4 confers its inhibitory effects on lipoprotein lipase by disrupting the enzyme dimerization[J]. J Biol Chem, 2009, 284(18): 11942-11952. DOI: 10.1074/jbc.M809802200.
26. Zhang R, Zhang K. An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues[J/OL]. Prog Lipid Res, 2022, 85: 101140[2022-11-16]. https://pubmed.ncbi.nlm.nih.gov/34793860/. DOI: 10.1016/j.plipres.2021.101140.
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Research progress on type 2 diabetic retinopathy in adolescents

Chinese Journal of Ocular Fundus Diseases

Research progress in the role and mechanism of angiopoietin-like protein in diabetic retinopathy

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