Angiogenic neovessels promote tissue hypoxia

Mishra, Anusha

doi:10.1073/pnas.1612427113

Cited by 7 publications

(12 citation statements)

References 21 publications

(16 reference statements)

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“…OIR is a hypoxia-induced angiogenesis model and a representative experimental model for several human neovascular retinal diseases. As it is acknowledged that the angiogenic blood vessels actually support the persistency of hypoxia in the tissue and lead to the progression of NV diseases instead of resolving the pathology (Mishra, 2016), it has become absolute necessity to understand their biology in detail. The most comprehensive proteomics-based analysis of the OIR to date delineates the possible molecular mechanisms that may drive angiogenesis in this model (Vähätupa et al, 2018a).…”

Section: Resultsmentioning

confidence: 99%

“…Finally, the vascular stabilizing functions of R-Ras also involve pericytes, as R-Ras is needed for their recruitment to the angiogenic blood vessels ) ( Figure 6). Pericyte loss, in turn, leads to pathological angiogenesis, and their loss is considered as a key feature in the progression of DR (Beltramo and Porta, 2013;Mishra, 2016). Our understanding on role of R-Ras as a master regulator of vascular permeability is currently increasing in diseased states.…”

Section: R-ras and Filamin A Axis In Vascular Stabilization Of Angiogmentioning

confidence: 99%

“…Furthermore, eradication of the neovessels by VEGF inhibitors may worsen the underlying ischemia and drive the formation of new, leaky blood vessels by alternative molecular mechanism. On the other hand, we have learned to understand that the persistency of angiogenic blood vessels leads to the progression of NV retinal diseases instead of resolving them (Mishra, 2016). Thus, the proposed molecular mechanism for future antiangiogenic therapies is one where the angiogenic blood vessels are "normalized" to stable ones to alleviate the hypoxia and stop the detrimental aberrant vascular leakage which leads scarring in retinal NV diseases (Goel et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

2020

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Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential anti-angiogenic factors for human diseases. We have recently performed the most comprehensive characterization of OIR by a relatively novel mass spectrometry (MS) technique, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS) proteomics and used genetically modified mice strains to identify novel molecular drug targets in angiogenic retinal diseases. We have confirmed the relevance of the identified molecular targets to human diseases by determining their expression pattern in neovascular membranes obtained from PDR and RVO patients. Based on our results, crystallins were the most prominent proteins induced by early hypoxic environment during the OIR, while actomyosin complex and Filamin A-R-Ras axis, that regulates vascular permeability of the angiogenic blood vessels, stood out at the peak of angiogenesis. Our results have revealed potential new therapeutic targets to address hypoxia-induced pathological angiogenesis and the associated vascular permeability in number of retinal diseases.

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Section: Resultsmentioning

confidence: 99%

Section: R-ras and Filamin A Axis In Vascular Stabilization Of Angiogmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

2020

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“…It is known that the vascular endothelial growth factor-A (VEGF) plays an integral role in causing pathological angiogenesis and vascular leakage [3]. When the cells of the retina experience hypoxia, the transcription factor hypoxia inducible factor-1α (HIF-1α) is stabilized [4][5][6][7][8]. Stabilized HIF-1α translocates to the cell nucleus and forms a complex with HIF-1β.…”

Section: Introductionmentioning

confidence: 99%

Selective Targeting and Tissue Penetration to the Retina by a Systemically Administered Vascular Homing Peptide in Oxygen Induced Retinopathy (OIR)

et al. 2021

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Pathological angiogenesis is the hallmark of ischemic retinal diseases among them retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and a widely used model for ischemic retinopathies. We explored whether the vascular homing peptide CAR (CARSKNKDC) which recognizes angiogenic blood vessels can be used to target the retina in OIR. We were able to demonstrate that the systemically administered CAR vascular homing peptide homed selectively to the preretinal neovessels in OIR. As a cell and tissue-penetrating peptide, CAR also penetrated into the retina. Hyperoxia used to induce OIR in the retina also causes bronchopulmonary dysplasia in the lungs. We showed that the CAR peptide is not targeted to the lungs in normal mice but is targeted to the lungs after hyperoxia-/hypoxia-treatment of the animals. The site-specific delivery of the CAR peptide to the pathologic retinal vasculature and the penetration of the retinal tissue may offer new opportunities for treating retinopathies more selectively and with less side effects.

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“…O processo angiogênico, portanto, depende do equilíbrio entre fatores pró-angiogênicos e antiangiogênicos, bem como outras quimiocinas que permitem o recrutamento de células e pericitos endoteliais, e sua diferenciação em vasos sanguíneos no nicho tumoral (MISHRA, 2016…”

Section: Angiogêneseunclassified

Síntese e caracterização pré-clínica de um novo derivado de 2-nitroimidazol como potencial traçador PET para imagem de hipóxia tumoral

Nario¹

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Agradeço em primeiro lugar a meu orientador Dr. Emerson Soares Bernardes, o meu sincero agradecimento pela confiança, pelos ensinamentos transmitidos, pela amizade e sobretudo pela compreensão e conversa nas horas em que parece que nada está dando certo. Aos meus pais, Orlando e Milagros, como exemplos de dignidade, força, por ser os melhores pais do mundo e meu exemplo a seguir sempre, são a base para que eu chegasse até esta etapa de minha vida. À minha única e querida irmã, a força e luz da minha vida sem ela impossível chegar até aqui, pela amizade, amor e companheirismo ao longo de nossas vidas. Eu não seria absolutamente nada sem você! À minha namorada Yanexy Guerrero Pérez, por estar ao meu lado nesses últimos anos de tanto estresse, obrigado por muito amor, força, carinho e compreensão nos bons e maus momentos. Amo você! À Dra. Sofia de Nascimento, pelo incentivo durante a realização deste trabalho, por sua ajuda em vários experimentos e sua valiosa contribuição para a análise e discussão dos resultados.

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Angiogenic neovessels promote tissue hypoxia

Cited by 7 publications

References 21 publications

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

Selective Targeting and Tissue Penetration to the Retina by a Systemically Administered Vascular Homing Peptide in Oxygen Induced Retinopathy (OIR)

Síntese e caracterização pré-clínica de um novo derivado de 2-nitroimidazol como potencial traçador PET para imagem de hipóxia tumoral

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