Animal models for anti-angiogenic therapy in endometriosis

The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis.

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“…9,12 The present study now demonstrates, for the first time, that this process is promoted by estrogen.…”

Section: Discussionsupporting

confidence: 70%

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

Rudzitis‐Auth

Nenicu

Nickels

et al. 2016

The American Journal of Pathology

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“…50 These compounds can be classified as either exclusive antiangiogenic agents, which only one known function is the suppression of angiogenesis, or inclusive agents that have anti-angiogenic activity associated with other functions.…”

Section: Therapeutic Trialsmentioning

confidence: 99%

Angiogenesis as a Therapeutic Target in Endometriosis

Djokovic

Calhaz‐Jorge

2014

Acta Med Port

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RESUMOIntrodução: A angiogénese é um factor determinante no estabelecimento e desenvolvimento das lesões de endometriose. Material e Métodos:Foram revistos os artigos indexados na PubMed e incluídos os estudos mais relevantes, publicados até Janeiro de 2014, sobre a angiogénese nas lesões de endometriose e/ou estratégias anti-angiogénicas para o tratamento desta doença ginecológica.Resultados: O presente artigo fornece um resumo conciso dos mecanismos moleculares conhecidos que promovem a vascularização das lesões de endometriose, podendo servir como alvos terapêuticos potenciais. Apresenta-se também uma revisão sistemática dos agentes anti-angiogénicos, inclusivos e exclusivos, que já foram avaliados em culturas de células, modelos animais e/ou doentes com endometriose. Discussão e Conclusão: A integração das estratégias anti-angiogénicas na terapêutica multimodal de endometriose será condicionada pelos resultados de avaliações futuras da verdadeira eficácia desses tratamentos, do risco de desenvolvimento de resistência aos medicamentos e da incidência de efeitos colaterais inaceitáveis. Palavras-chave: Inibidores da Angiogénese/uso terapêutico; Endometriose/terapêutica. ABSTRACT Introduction:Angiogenesis is a key factor for the successful establishment and growth of endometriotic lesions. Material and Methods:We performed a literature search in PubMed and reviewed the most pertinent studies published until January 2014 and focused on the endometriosis-associated angiogenesis and/or anti-angiogenic strategies for the treatment of this gynecological disorder. Results:The present review provides a concise summary of the known molecular mechanisms that promote vascularization of endometriotic lesions and may serve as potential therapeutic targets. We also present a systematic overview of the inclusive and exclusive anti-angiogenic agents that have been already studied in cell cultures, animal models and/or endometriosis patients. Discussion and Conclusion:The integration of anti-angiogenic approaches in the multimodal management strategies for endometriosis patients will be conditioned by the outcomes of future assessments regarding the effectiveness of such treatments, the risk of drug resistance development and the incidence of unacceptable side effects.

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“…According to various authors, however, there is a risk of cumulative adverse effects by combining several drugs that inhibit angiogenesis [48][49][50]. Nevertheless, the concept of a combination of various inhibitors opens up new perspectives in the therapy of endometriosis.…”

Section: Prevention Of Relapse (For Surgery)mentioning

confidence: 99%

Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis

Sheveleva¹,

Bejenar

Комличенко

et al. 2016

Gynecological Endocrinology

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Endometriosis is a chronic, progressive, relapsing estrogen-dependent disorder characterized by the growth of tissue structure and function similar to the endometrium outside the normal mucosa of the uterine cavity localization. Endometriosis is found in 10-15% of women in reproductive age and it is one of the main causes of pelvic pain syndrome and infertility. Mechanisms of the development of endometriosis and related pathological pain impulses are still poorly understood and therapeutic approaches do not always have a sufficient effect; in this connection, the study of the pathogenesis of endometriosis and endometriosis-associated pain currently is perspective. Identification of significant factors of angiogenesis, lymphangiogenesis, and neurogenesis in the external genital endometriosis will promote the development of non-invasive early diagnosis and pathogenetic therapy.

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Animal models for anti-angiogenic therapy in endometriosis

Cited by 35 publications

References 109 publications

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions

Angiogenesis as a Therapeutic Target in Endometriosis

Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis

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