Angiogenesis as a Therapeutic Target in Endometriosis

Abstract

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.

Pathogenesis of deep endometriosis

“…For many other factors it remains unclear whether they are the cause or the consequence of endometriosis. Pelvic endometriosis is associated with a low-grade inflammation of the peritoneal cavity with higher concentrations of activated macrophages and thus with higher concentrations of the many different cytokines (68-72) and angiogenic factors (73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91). The many immunologic disturbances were recently reviewed (92)(93)(94)(95)(96)(97)(98)(99).…”

Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: A preliminary study

“…The roles of EGR1and EGR3 in angiogenesis has also recently been recognized and were considered to regulate certain important angiogenic factors, such as vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2, and C-X-C motif chemokine ligand 1. Angiogenesis is considered to be pivotal to the implant and growth of endometriotic lesions in the pelvic microenvironment (30). The endometrium, which contains robust stem cell populations and striking regenerative ability, is a rich source of angiogenic factors (31).…”

Bioinformatics strategy for the screening of key genes to differentiate adenomyosis from endometriosis (Review)

“…Angiogenesis (1 gene). Ectopic endometriotic lesions produce multiple pro-angiogenic factors, including VEGF, angiopoietin (Ang)-1 and Ang-2, PDGF, IL-1β, IL-6 and IL-8, TNF-α, and TGF-β, Notch and HIF-1α that were also upregulated in eutopic endometrium from patients with endometriosis in comparison with endometrium from healthy women (122). HIF-1α represents a key regulator of angiogenesis.…”