Vascular adhesion protein‐1 blockade suppresses choroidal neovascularization

Noda, Kousuke; She, Haicheng; Nakazawa, Toru; Hisatomi, Toshio; Nakao, Shintaro; Almulki, L.; Zandi, Souska; Miyahara, Shinya; Ito, Yasuhiro; Thomas, Kerry; Garland, Robert; Miller, Joan W.; Gragoudas, Evangelos S.; Mashima, Yukihiko; Hafezi-Moghadam, Ali

doi:10.1096/fj.07-105346

Cited by 53 publications

(64 citation statements)

References 40 publications

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“…This finding supports previous reports revealing the key role of VAP-1 in angiogenesis-related diseases, including cancer 13 and age-related macular degeneration. 5 To date, molecular diagnosis has not been introduced to patient care and need is great for in vivo molecular markers of angiogenic disease. Our results reveal that VAP-1 might become a useful diagnostic target for inflammatory and angiogenic diseases.…”

Section: Discussionmentioning

confidence: 99%

“…16 However, whether VAP-1 is expressed in lymphatics and whether it contributes to lymphangiogenesis is unknown. 2,5,17,18 …”

Section: Il-1␤-inducedmentioning

confidence: 99%

“…1 Recently, we reported the expression of VAP-1 in the human eye 2 and the critical role it plays in ocular inflammatory diseases, such as uveitis, 3 age-related macular degeneration, 4 and diabetic retinopathy. 5 IL-1␤, a multipotent cytokine, is critically involved in the acute inflammatory response, activation and chemotaxis of inflammatory and antigen-presenting cells, up-regulation of adhesion molecules, and neovascularization. 6 IL-1␤ induces lymph-and angiogenesis and leukocyte infiltration.…”

mentioning

confidence: 99%

“…10 Leukocyte recruitment is critical for lymph-and angiogenesis. 8,11,12 VAP-1 inhibition reduces pathological angiogenesis by diminishing macrophage infiltration 5 but is not involved in physiologic vessel formation. 13 VAP-1 contributes to tumor angiogenesis but not lymphangiogenesis through its impact on leukocytes recruitment.…”

mentioning

confidence: 99%

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VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

Nakao

Noda

Zandi

et al. 2011

The American Journal of Pathology

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Vascular adhesion protein-1 (VAP-1) contributes to inflammatory and angiogenic diseases, including cancer and age-related macular degeneration. It is expressed in blood vessels and contributes to inflammatory leukocyte recruitment. The cytokines IL-1␤ and vascular endothelial growth factor A (VEGF-A) modulate angiogenesis, lymphangiogenesis, and leukocyte infiltration. The lymphatic endothelium expresses intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, which facilitate leukocyte transmigration into the lymphatic vessels. However, whether lymphatics express VAP-1 and whether they contribute to cytokine-dependent lymph-and angiogenesis are unknown. We investigated the role of VAP-1 in IL-1␤-and VEGF-A-induced lymph-and angiogenesis using the established corneal micropocket assay. IL-1␤ increased VAP-1 expression in the inflamed cornea. Our in vivo molecular imaging revealed significantly higher VAP-1 expression in neovasculature than in the preexisting vessels. VAP-1 was expressed in blood but not lymphatic vessels in vivo. IL-1␤-induced M2 macrophage infiltration and lymphand angiogenesis were blocked by VAP-1 inhibition. In contrast, VEGF-A-induced lymph-and angiogenesis were unaffected by VAP-1 inhibition. Our results indicate a key role for VAP-1 in lymph-and angiogenesisrelated macrophage recruitment. VAP-1 might become a new target for treatment of inflammatory lymph-and angiogenic diseases, including cancer.

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Section: Discussionmentioning

confidence: 99%

“…16 However, whether VAP-1 is expressed in lymphatics and whether it contributes to lymphangiogenesis is unknown. 2,5,17,18 …”

Section: Il-1␤-inducedmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

Nakao

Noda

Zandi

et al. 2011

The American Journal of Pathology

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“…18 Using a 532-nm laser (Oculight GLx; Iridex, Mountain View, CA) , a slit-lamp delivery system, and a cover glass as a contact lens, four spots were placed in each eye. The parameters were 100 mW, 50 m, and 100 ms in mice and 150 mW, 100 m, 100 ms in rats.…”

Section: Laser-induced Cnvmentioning

confidence: 99%

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Lara-Castillo

Zandi

Nakao

et al. 2009

The American Journal of Pathology

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Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however , its role in vascular leakage and angiogenesis is unknown. In vitro , retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 mol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGFinduced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP's effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP's TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum , ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role , such as age-related macular degeneration or diabetic retinopathy.

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Differential proteomic analysis of white adipose tissues from T2D KKAy mice by LC‐ESI‐QTOF

Zhu

et al. 2017

Proteomics

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Type 2 diabetes (T2D) has become a worldwide increasingly social health burden for its high morbidity and heightened prevalence. As one of the main tissues involved in uptake of glucose under the stimulation of insulin, WAT plays very important role in metabolic and homeostasis regulation. We performed a differential proteomics study to investigate alterations in epididymis fat pad of high fat diet fed T2D KKAy mice compared to normal fed C57BL/6J mice, by O-labeling relative quantitative technique. Among 329 confidently identified proteins, 121 proteins showed significant changes with CV ≤ 20% (fold changes of>2 or <0.5 as threshold). According to GO classification, we found that altered proteins contained members of biological processes of metabolic process, oxidative stress, ion homeostasis, apoptosis and cell division. In metabolic, proteins assigned to fatty acid biosynthesis (FAS etc.) were decreased, the key enzyme (ACOX3) in β-oxidation process was increased. Increased glycolysis enzymes (ENOB etc.) and decreased TCA cycle related enzymes (SCOT1 etc.) suggested that glucose metabolism in mitochondria of T2D mice might be impaired. Elevated oxidative stress was observed with alterations of a series of oxidordeuctase (QSOX1 etc.). Besides, alterations of ion homeostasis (AT2C1 etc.) proteins were also observed. The enhancement of cell proliferation associated proteins (ELYS etc.) and inhibition of apoptosis associated proteins (RASF6 etc.) in WAT might contributed to the fat pad and body weight gain. Overall, these changes in WAT may serve as a reference for understanding the functional mechanism of T2D.

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Vascular adhesion protein‐1 blockade suppresses choroidal neovascularization

Cited by 53 publications

References 40 publications

VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Differential proteomic analysis of white adipose tissues from T2D KKAy mice by LC‐ESI‐QTOF

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