Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis

Zhou, Haiyan; Chen, Tangting; Li, Yongjie; You, Jingcan; Deng, Xin; Chen, Ni; Li, Tian; Zheng, Yinggan; Li, Rong; Luo, Mao; Wu, Jianbo; Wang, Liqun

doi:10.3390/ijms23137137

Cited by 7 publications

(5 citation statements)

References 39 publications

(59 reference statements)

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“…AGEs during chronic hyperglycemia may modify Tie2 and upregulate both VEGF and Ang2 mRNA in EC [25,122]. Glycation of Tie2 by AGE products inhibits Ang1induced Tie2 autophosphorylation and Akt downstream signaling.…”

Section: Effects Of Hyperglycemia and Ang-tie Signalingmentioning

confidence: 99%

“…At the molecular level, several animal models implicate the angiopoietins and Tie2 in the pathogenesis of DR [23][24][25][26][27][28]. Hyperglycemia induces Ang2 upregulation in both retinal EC in vitro and in diabetic animals prior to any morphological changes in the retinal capillaries [28,48].…”

Section: Effects Of Hyperglycemia and Ang-tie Signalingmentioning

confidence: 99%

“…Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used [19]. Since the discovery of the angiopoietins (Ang) and their respective tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Tie) receptors in the 1990's [20][21][22], mounting evidence has implicated the angiopoietin-Tie signaling pathway in the pathogenesis of DR [23][24][25][26][27][28]. Targeting the Tie signaling pathway may improve the outcomes of patients with DR.…”

Section: Introductionmentioning

confidence: 99%

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Beyond VEGF: Angiopoietin–Tie Signaling Pathway in Diabetic Retinopathy

Chen-Li,

Martinez-Archer,

Coghi

et al. 2024

JCM

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Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin–Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

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Section: Effects Of Hyperglycemia and Ang-tie Signalingmentioning

confidence: 99%

Section: Effects Of Hyperglycemia and Ang-tie Signalingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Beyond VEGF: Angiopoietin–Tie Signaling Pathway in Diabetic Retinopathy

Chen-Li,

Martinez-Archer,

Coghi

et al. 2024

JCM

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show abstract

“…Angiopoietin (Ang) ligand and Tie (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains-1) receptor tyrosine kinases are essential for maintaining static EC and vascular homeostasis. 86 , 87 Ang belongs to a family of growth factors necessary for blood vessel development. There are four varieties of Ang: Ang-1, Ang-2, Ang-3, and Ang-4.…”

Section: Important Bioactive Moleculesmentioning

confidence: 99%

Therapeutic angiogenesis based on injectable hydrogel for protein delivery in ischemic heart disease

Wang¹,

Song²,

Xie³

et al. 2023

iScience

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“…Another interesting article in this issue reports the role of glycation in inhibiting angiopoietin-1 signaling activation and angiopoietin-1-induced angiogenesis. This study highlights the potential for post-translational modifications of proteins to play a key role in regulating angiogenesis, and suggests that these modifications may be promising targets for the development of new therapies [ 5 ]. Furthermore, another article describes a novel high-content angiogenesis assay that reveals how lacidipine, an L-type calcium channel blocker, induces vascular lumen expansion in vitro.…”

mentioning

confidence: 99%