Mechanism of retinal pericyte migration through Angiopoietin/Tie-2 signaling pathway on diabetic rats

Dewi, Nadia Artha; Aulanni’am, Aulanni’am; Sujuti, Hidayat; Widodo, M. Aris; Soeatmadji, Djoko Wahono

doi:10.18240/ijo.2018.03.05

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…Ang-2 overexpression under pathological conditions, such as hyperglycaemia, mediates integrin-mediated pericyte detachment and apoptosis [ 28 , 50 ], which destabilises the retinal vasculature [ 63 ]. In a transgenic mouse model with experimentally induced DR, Ang-2 overexpression (in mOpsinhAng2 mice) increased the number of circulating pericytes in diabetic retinas by 2.3 fold versus non-diabetic retinas (non-diabetic wild-type: 51 ± 7 and diabetic mOpsinhAng2 mice: 118 ± 25 pericyte per mm 2 of capillary area; P < 0.0001).…”

Section: The Ang/tie Signalling Pathway In Angiogenesismentioning

confidence: 99%

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Joussen

Ricci

Paris

et al. 2021

Eye

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The angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) pathway is an emerging key regulator in vascular development and maintenance. Its relevance to clinicians and basic scientists as a potential therapeutic target in retinal and choroidal vascular diseases is highlighted by recent preclinical and clinical evidence. The Ang/Tie pathway plays an important role in the regulation of vascular stability, in angiogenesis under physiological and pathological conditions, as well as in inflammation. Under physiological conditions, angiopoietin-1 (Ang-1) binds to and phosphorylates the Tie2 receptor, leading to downstream signalling that promotes cell survival and vascular stability. Angiopoietin-2 (Ang-2) is upregulated under pathological conditions and acts as a context-dependent agonist/antagonist of the Ang-1/Tie2 axis, causing vascular destabilisation and sensitising blood vessels to the effects of vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A synergistically drive vascular leakage, neovascularisation and inflammation, key components of retinal vascular diseases. Preclinical evidence suggests that modulating the Ang/Tie pathway restores vascular stabilisation and reduces inflammation. This review discusses how targeting the Ang/Tie pathway or applying Ang-2/VEGF-A combination therapy may be a valuable therapeutic strategy for restoring vascular stability and reducing inflammation in the treatment of retinal and choroidal vascular diseases.

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Section: The Ang/tie Signalling Pathway In Angiogenesismentioning

confidence: 99%

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Joussen

Ricci

Paris

et al. 2021

Eye

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“…However, studies in diabetic mouse models support that Ang-2 induces pericyte migration through the Tie-2 receptor, specifically the Ras-dependent extracellular signal-regulated kinase (ERK1/2) and serine and threonine kinase/protein kinase B (Akt/PKB) pathways. ERK1/2, the dominant pathway, suppresses other pathway activities and increases pericyte migration [ 32 ]. While these findings are promising, further studies are required to characterize this mechanism better.…”

Section: Angiopoietin Biology and Signaling Literature Reviewmentioning

confidence: 99%

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

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This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

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“…This is due to the binding of angiopoietin-1/2 from endothelial cells to Tie-2 receptors on pericytes. Thereby, signals are generated to induce pericytes to separate from the blood vessels to initiate angiogenesis [ 96 – 98 ]. After pericytes are detached, matrix metalloproteinases and proteases change the extracellular matrix, enabling pericytes to undergo cell migration [ 99 ].…”

Section: The Mechanism Of Angiogenesis After Myocardial Infarctionmentioning

confidence: 99%

Natural Herbal Medicine as a Treatment Strategy for Myocardial Infarction through the Regulation of Angiogenesis

Zhang

Song

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Aim of Study. Myocardial infarction is the number one cause of death worldwide. Existing treatment methods such as drugs and surgery cannot completely restore the structure and function of the ischemic heart. In recent years, therapeutic angiogenesis has received gradually increasing attention due to its fundamental therapeutic advantages of improving microcirculation and restoring blood supply in ischemic areas. This article mainly reviewed the mechanism and effect of angiogenesis-promoting herbs. Methods. We conducted a literature search on the bioactive components of medicinal plants and their effects on angiogenesis after MI. We searched for articles in Web of Science, MEDLINE, PubMed, Scopus, Google Scholar, and China National Knowledge Infrastructure databases before April 2021. Results. In this article, we summarized the mechanisms by which copper ions, microRNA, Akt1, inflammation, oxidative stress, mitochondria, and pericytes are involved in angiogenesis after myocardial infarction. In addition, we reviewed the angiogenic effects of natural herbal medicines such as Salvia miltiorrhiza Bunge Bunge, Carthamus tinctorius L., Pueraria lobata, Astragalus, Panax ginseng C.A. Mey., Panax notoginseng (Burkill) F.H. Chen, Cinnamomum cassia (L.) J. Presl, Rehmannia glutinosa (Gaertn.) DC., Leonurus japonicus Houtt, Scutellaria baicalensis Georgi., and Geum macrophyllum Willd. Conclusions. Some herbs have the effect of promoting angiogenesis. In the future, natural proangiogenic drugs may become candidates for the treatment of cardiovascular diseases.

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Mechanism of retinal pericyte migration through Angiopoietin/Tie-2 signaling pathway on diabetic rats

Abstract: Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERK1/2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.

Cited by 4 publications

References 20 publications

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Natural Herbal Medicine as a Treatment Strategy for Myocardial Infarction through the Regulation of Angiogenesis

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