Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis

Akwii, Racheal G; Sajib, Sanaullah; Zahra, Fatema Tuz; Tullar, Paul; Zabet-Moghaddam, Masoud; Zheng, Yi; Gutkind, J. Silvio; Doçi, Colleen L.; Mikelis, Constantinos M.

doi:10.1007/s10456-022-09831-y

Cited by 17 publications

(10 citation statements)

References 123 publications

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“…The lymph drains back into the blood circulation near the heart. The assembly of the lymphatic system occurs during embryonic development through coordinated mechanisms involving precursor cells [110] and epigenetic pathways [111], some of which are recapitulated during lymphatic neogenesis (such as in cancer) [112][113][114][115][116][117]. The identification of a number of lymphaticselective molecular markers such as podoplanin, VEGFR3, LYVE-1, and PROX-1, has enabled detailed studies of the lymphatic vasculature and lymphangiogenesis [118][119][120].…”

Section: Lymphangiogenesismentioning

confidence: 99%

Pathological angiogenesis: mechanisms and therapeutic strategies

Dudley

2023

Angiogenesis

118

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In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but are often done so without the normal feedback mechanisms that regulate the ordinary spatial and temporal patterns of blood vessel formation. Thus, pathological angiogenesis presents new challenges yet new opportunities for the design of vascular-directed therapies. Here, we provide an overview of recent insights into blood vessel development and highlight novel therapeutic strategies that promote or inhibit the process of angiogenesis to stabilize, reverse, or even halt disease progression. In our review, we will also explore several additional aspects (the angiogenic switch, hypoxia, angiocrine signals, endothelial plasticity, vessel normalization, and endothelial cell anergy) that operate in parallel to canonical angiogenesis mechanisms and speculate how these processes may also be targeted with anti-angiogenic or vascular-directed therapies.

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Section: Lymphangiogenesismentioning

confidence: 99%

Pathological angiogenesis: mechanisms and therapeutic strategies

Dudley

2023

Angiogenesis

118

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“…ANGPT2 belongs to the endothelial growth factor angiopoietin family and is significantly upregulated at sites of vascular remodeling [ 64 ]. Mechanistically, ANGPT2 can act on the cytoskeleton of ECs to induce migration [ 65 ]. Knockdown of ANGPT2 leads to a lack of tip cells in the anterior part of neointimal sprouts in the mouse retina [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization

Shen,

Lin,

et al. 2023

J Neuroinflammation

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Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization. Graphical Abstract

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“…The activation of RhoA led to the phosphorylation of the downstream effectors ROCK and formins, thereby regulating lymphangiogenesis. 323 …”

Section: Therapeutic Interventions and Clinical Research Progress Of ...mentioning

confidence: 99%

Lymphatic vessel: Origin, heterogeneity, biological functions and therapeutic targets

Hu,

Zhao,

et al. 2024

Sig Transduct Target Ther

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Lymphatic vessels, comprising the secondary circulatory system in human body, play a multifaceted role in maintaining homeostasis among various tissues and organs. They are tasked with a serious of responsibilities, including the regulation of lymph absorption and transport, the orchestration of immune surveillance and responses. Lymphatic vessel development undergoes a series of sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into the highly specialized lymphatic vessel networks. Lymphangiogenesis, as defined by new lymphatic vessels sprouting from preexisting lymphatic vessels/embryonic veins, is the main developmental mechanism underlying the formation and expansion of lymphatic vessel networks in an embryo. However, abnormal lymphangiogenesis could be observed in many pathological conditions and has a close relationship with the development and progression of various diseases. Mechanistic studies have revealed a set of lymphangiogenic factors and cascades that may serve as the potential targets for regulating abnormal lymphangiogenesis, to further modulate the progression of diseases. Actually, an increasing number of clinical trials have demonstrated the promising interventions and showed the feasibility of currently available treatments for future clinical translation. Targeting lymphangiogenic promoters or inhibitors not only directly regulates abnormal lymphangiogenesis, but improves the efficacy of diverse treatments. In conclusion, we present a comprehensive overview of lymphatic vessel development and physiological functions, and describe the critical involvement of abnormal lymphangiogenesis in multiple diseases. Moreover, we summarize the targeting therapeutic values of abnormal lymphangiogenesis, providing novel perspectives for treatment strategy of multiple human diseases.

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Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis

Cited by 17 publications

References 123 publications

Pathological angiogenesis: mechanisms and therapeutic strategies

Pathological angiogenesis: mechanisms and therapeutic strategies

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization

Lymphatic vessel: Origin, heterogeneity, biological functions and therapeutic targets

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