Angiogenesis and Endometriosis

Abstract

A comprehensive review was performed to survey the role of angiogenesis in the pathogenesis of endometriosis. This is a multifactorial disease in which the development and maintenance of endometriotic implants depend on their invasive capacity and angiogenic potential. The peritoneal fluid of patients with endometriosis is a complex suspension carrying inflammatory cytokines, growth factors, steroid hormones, proangiogenic factors, macrophages, and endometrial and red blood cells. These cells and their signaling products concur to promote the spreading of new blood vessels at the endometriotic lesions and surroundings, which contributes to the endometriotic implant survival. Experimental studies of several antiangiogenic agents demonstrated the regression of endometriotic lesions by reducing their blood supply. Further studies are necessary before these novel agents can be introduced into clinical practice, in particular the establishment of the safety of anti-angiogenic medications in women who are seeking to become pregnant.

Angiogenesis as a Therapeutic Target in Endometriosis

“…They are: (I) sprouting of novel capillary blood vessels from the pre-existing vasculature, a process called angiogenesis; [7][8][9] (II) splitting of a single pre-existing vessel in two new vascular segments through the insertion of a tissue pillar, i.e. vascular intussusceptions; 10,11 (III) elongation/ widening of pre-existing vessels; 12,13 and (IV) incorporation of circulating endothelial progenitor cells (EPCs) into vessels, a mechanism denominated vasculogenesis.…”

“…4 Many other ubiquitously expressed molecules have been found to enhance angiogenesis in vitro, in animal models of endometriosis and/ or in human samples. 12,[36][37][38][39][40] Such promoters include cytokines and growth factors secreted by immune and neuroendocrine cells (e.g., interleukins, IL-1β, 6 and 8, tumor necrosis factor-α, TNF-α, and transforming growth factor β, TGF-β). Finally, not only the secreted factors but also several membranebound proteins, that mediate tumor angiogenesis, are likely engaged in the endometriotic neovascularization, such as Dll4/Notch, vascular integrins and ephrins/Eph receptors.…”

Polymorphisms in VEGF and KDR genes in the development of endometriosis: a systematic review

“…The angiogenesis, through VEGF-KDR signals, is an important event in the development of the disease, 11,12 since endometriosis lesions are characterized by a dense vascularization and requires blood supply suitable for survival. 11 Furthermore, an increased expression of VEGF and VEGFR-2 in samples of women with endometriosis was observed when compared to its control. 12 The expression of VEGF and KDR genes as well as the activity of these proteins may be modified by the presence of polymorphisms in coding regions and non-coding genes.…”

“…For this to occur, the angiogenesis process is essential and it is characterized by the growth of new blood vessels from pre-existing ones. 11 Among the pro-angiogenic factors, the vascular endothelial growth factor (VEGF) is highlighted and plays an important role in the development of endometriosis. 11 In 2008, our group observed an increased distribution of VEGF and its receptor VEGFR-2 in samples of endometriosis of the ovary, bladder and the recto-sigmoid, when it was compared to control and the largest distribution of VEGF and VEGFR-2 was observed in the endometriosis of the recto-sigmoid,which is the most severe.…”

“…11 Among the pro-angiogenic factors, the vascular endothelial growth factor (VEGF) is highlighted and plays an important role in the development of endometriosis. 11 In 2008, our group observed an increased distribution of VEGF and its receptor VEGFR-2 in samples of endometriosis of the ovary, bladder and the recto-sigmoid, when it was compared to control and the largest distribution of VEGF and VEGFR-2 was observed in the endometriosis of the recto-sigmoid,which is the most severe. 12 VEGF is encoded by a gene with the same name, located on chromosome 6p21.3, composed by eight exons, 13 while its receptor VEGFR-2 is encoded by KDR gene (kinase insert domain receptor), located on chromosome 4q11-q12, composed by 30 exons.…”