Studying molecular signaling in major angiogenic diseases

Nathan, Jhansi; Shameera, Rabiathul; Gajalakshmi, Palanivel

doi:10.1007/s11010-022-04452-x

Cited by 5 publications

(3 citation statements)

References 125 publications

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“…For example, vegf is a commonly known gene for promoting neovascularity and binds to the receptor vegfr or co‐receptor nrp1 in cell membrane to initiate angiogenesis (Lyu et al, 2020). Also, the stimulus for the expression vegf gene may come from environmental hypoxia ( hif‐1 ) or other pathological condition (Nathan et al, 2022). Additionally, the expression of inos and cox‐2 has been reported in angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Role of berberine on angiogenesis and blood flow hemodynamics using zebrafish model

Nathan,

Shameera,

Devarajan

et al. 2023

J of Applied Toxicology

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Angiogenesis and hemodynamic instability created by the irregular blood vessels causes hypoperfusion and angiogenesis‐mediated diseases. Therefore, therapies focusing on controlling angiogenesis will be a valuable approach to treat a broad spectrum of diseases. In this study, we explored the anti‐angiogenic potential of berberine (BBR) and also analyzed blood flow hemodynamics using zebrafish embryos. Zebrafish embryos treated with BBR (0.01–0.75 mM) at various doses at 1 hour post‐fertilization (hpf) developed a variety of phenotypic variations including aberrant blood vessels, tail bending, edema, and hemorrhage. Survival rates were much lower at higher dosages, and hatching rates were almost 99%, whereas control group appeared normal. Heart rate is an essential measure that has a strong association with hemodynamics. We used ImageJ software to study the heart rate of embryos treated with BBR, preceded by video processing. The resultant graph shows a significant decrease in heart rate of embryos treated with BBR in dose‐dependent manner. Also, RBC staining using o‐Dianisidine confirms the anti‐angiogenic potential of BBR by indicating the decrease in the intersegmental vessels at 0.5 and 0.75 mM treated embryos. Further, the gene expression study determined that the transcripts (vegf, vegfr2, nrp1a, hif‐1α, nos2a, nos2b, cox‐2a, and cox‐2b) measured were found to be downregulated by BBR at 0.5 mM concentration, from which we conclude that enos/vegf signaling could play an important role in modulating angiogenesis. Our data imply that BBR may be an effective compound for suppressing angiogenesis in vivo, which might be helpful in the treatment of vascular disorders like cancer and diabetic retinopathy in future.

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Section: Introductionmentioning

confidence: 99%

Role of berberine on angiogenesis and blood flow hemodynamics using zebrafish model

Nathan,

Shameera,

Devarajan

et al. 2023

J of Applied Toxicology

Self Cite

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“…ahr1a and ahr1b were also significantly downregulated in Tg( drl : hoxa9 ; hsp70 : meis1 ), consistent with the previous finding showing that diminished AHR signalling drives human AML stem cell maintenance [ 48 , 49 ]. Other downregulated genes were tmem88a , trim2a , ephB4 , jag2b , notch3 and unc5b , which are known to regulate vascular development [ 50 ]. We validated the expression of the representative genes by qPCR assay ( figure 5 e ).…”

Section: Resultsmentioning

confidence: 99%

Hoxa9 / meis1 -transgenic zebrafish develops acute myeloid leukaemia-like disease with rapid onset and high penetrance

Wang

Huang

et al. 2022

Open Biol.

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HOXA9 and MEIS1 are co-expressed in over 50% of acute myeloid leukaemia (AML) and play essential roles in leukaemogenesis, but the mechanisms involved are poorly understood. Diverse animal models offer valuable tools to recapitulate different aspects of AML and link in vitro studies to clinical trials. We generated a double transgenic zebrafish that enables hoxa9 overexpression in blood cells under the draculin ( drl ) regulatory element and an inducible expression of meis1 through a heat shock promoter. After induction, Tg( drl : hoxa9 ; hsp70 : meis1 ) embryos developed a preleukaemic state with reduced myeloid and erythroid differentiation coupled with the poor production of haematopoietic stem cells and myeloid progenitors. Importantly, most adult Tg( drl : hoxa9 ; hsp70 : meis1 ) fish at 3 months old showed abundant accumulations of immature myeloid precursors, interrupted differentiation and anaemia in the kidney marrow, and infiltration of myeloid precursors in peripheral blood, resembling human AML. Genome-wide transcriptional analysis also confirmed AML transformation by the transgene. Moreover, the dihydroorotate dehydrogenase (DHODH) inhibitor that reduces leukaemogenesis in mammals effectively restored haematopoiesis in Tg( drl : hoxa9 ; hsp70 : meis1 ) embryos and improved their late survival. Thus, Tg( drl : hoxa9 ; hsp70 : meis1 ) zebrafish is a rapid-onset high-penetrance AML-like disease model, which provides a novel tool to harness the unique advantages of zebrafish for mechanistic studies and drug screening against HOXA9 / MEIS1 overexpressed high-risk AML.

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“…The angiogenetic pathology usually commences from so-called “angiogenic switch”, a process describing the imbalanced tilt between proangiogenic and antiangiogenic regulators toward activators, leading to the recruitment of independent blood supply in malignancies and dysregulation of tissue vascularization in other diseases, respectively 270 , 273 . Many excellent reviews are on hand describing dissect angiogenic mechanisms in different diseases, which will not be discussed here in detail 271 , 274 , 275 , 276 . The tumor-educated angiogenesis in malignancies is frequently manifested as upregulation of VEGF with significantly higher expression of VEGF in many types of solid tumors, probably resulting from tumor cell infiltration, metabolic alterations, and tissue hypoxia 271 , 277 .…”

Section: Lessons To Learn From Cancer Complications and Comorbiditiesmentioning

confidence: 99%

Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy

Mao,

Wu,

Huang

et al. 2024

Acta Pharmaceutica Sinica B

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Studying molecular signaling in major angiogenic diseases

Cited by 5 publications

References 125 publications

Role of berberine on angiogenesis and blood flow hemodynamics using zebrafish model

Role of berberine on angiogenesis and blood flow hemodynamics using zebrafish model

Hoxa9 / meis1 -transgenic zebrafish develops acute myeloid leukaemia-like disease with rapid onset and high penetrance

Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy

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