{"paper_id":"f1e13de5-c154-42d3-bed9-9eb8601990a7","body_text":"Copyright@ Xia P | Biomed J Sci & Tech Res| BJSTR. MS.ID.002798.\n11779\nMini Review\nISSN: 2574 -1241\nExploring the Relationship Between Endometriosis and \nVascular Health: A Systematic Mini-Review\nSantos JM1, Singh B2 and Xia P3*\n1Department of Post-Baccalaureate Premedical Program, USA\n2Johns Hopkins Medicine, Research \n3Department of Gynecology and Obstetrics, Baltimore, USA\n*Corresponding author: Ping Xia, Department of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, Maryland, USA\n DOI: 10.26717/BJSTR.2019.16.002798\nReceived: \n   March 07, 2019\nPublished: \n   March 18, 2019\nCitation: Santos JM, Singh B, Xia P . \nExploring the Relationship Between \nEndometriosis and Vascular Health: \nA Systematic Mini-Review . Biomed \nJ Sci & Tech Res 16(1)-2019. BJSTR. \nMS.ID.002798.\nARTICLE INFO abstract\nThe relationship between endometriosis and vascular health has been postulated \nover the past couple of years. Because the pathophysiology of endometriosis remains \nsomewhat unclear, there is great interest in this relationship. Due to the co-current \nnature of endometriosis, vasculature, and cardiovascular disease, several therapies \ngeared toward vascular-related processes (i.e. angiogenesis and atherosclerosis) have \nbeen proposed and/or studied. In this review paper, we discuss the evidence of five \narticles that support the correlation between endometriosis and vascular health and its \nclinical implications.\nIntroduction\nEndometriosis affects up to 50% of women with infertility [1]. \nIt is a costly disease with an estimated annual economic burden in \nthe United States of $78.05 billion in 2013 [2]. It is the presence \nof endometriotic lesions in extrauterine locations (e.g. pelvic \nperitoneum, ovaries, rectovaginal septum [3]. For the endometriotic \nlesions to plant itself and survive, it must establish its own \nblood supply- thus vascularization (i.e. angiogenesis) is a major \nhallmark in the pathogenesis of endometriosis [4]. Angiogenesis \nis initiated by angiogenic growth factors (e.g. vascular endothelial \ngrowth factor, VEGF), which have been extensively studied as it \nis heavily expressed in red endometriotic lesions [4]. In addition \nto angiogenesis, cardiovascular disease (e.g. atherosclerosis) has \nshown potential in characterizing endometriosis since it is a source \nof systemic subclinical inflammation [5]. Therefore, because of \nthe developing correlation between endometriosis and vascular, \ninterest in developing treatments focused on anti-angiogenics and \nanti-inflammatories have grown.\nMaterials and Methods \nSearch and Study Selection\nIn order to find clinical trials and/or review papers that support \nthe relationship between endometriosis and vascular health and \npossible treatments, the decision was made to search PubMed. \nBecause of the focus on the relationship between these two factors, \nthe search term “endometriosis and vascular health” was used. \nThis initially garnered 336 results, which were further filtered by \npublication dates within ten years. This filter narrowed down the \nsearch to 131 articles, which varied between clinical trials and \nreview papers. \nEligibility Criteria\nIn order to be eligible for review, the clinical trial and/or \nreview paper had to be published within the past ten years to \nensure relevancy of data and information that could be translated \nfor current use. Furthermore, the title of the articles had to include \n\nCopyright@ Xia P | Biomed J Sci & Tech Res| BJSTR. MS.ID.002798.\nVolume 16- Issue 1\nDOI: 10.26717/BJSTR.2019.16.002798\n11780\nendometriosis along with terms related to vascular health (e.g. \nantio-angiogenic, statin, vascular, atherosclerosis). \nResults\nAmongst the systemic search from PubMed, five articles were \neligible and included in this review paper. Two discussed the \nrelationship between endometriosis and vascular health, while \nthe remaining three discussed treatment options that focused on \na vascular cause (i.e. anti-angiogenics and anti-inflammatories). \nOf the five, four were review papers. The remaining article was a \nstudy. Two of the review papers discussed vascularization and \natherosclerosis in the context of endometriosis, while the other \ntwo review papers discussed treatment options that focused on \nvascularization. The study focused on proposing and supporting a \nvascular-associated treatment.\nDiscussion\nAngiogenesis\nMicroRNAs (miRNAs) may play important role in signaling \nnetwork regulating angiogenesis in endometriosis. Some have \nreported that they can control expression of angiogenic factors [6]. \nFurthermore, vasculogenesis incorporates circulating endothelial \nprogenitor cells (EPCs) from the bone marrow into the microvascular \nendothelium of newly developing micro vessels. These EPCs \ncontribute to the formation of new blood vessels (e.g. tumors, \nMIs, stroke) as well as vascularization of endometrium. Often \ntimes EPCs are recruited in the microvasculature of endometriotic \nlesions and regulated by VEGF and possible estrogen. Therefore, \na potential treatment would focus on gene therapy (e.g. miRNAs) \ntargeting angiogenesis and reducing the micro vessel density of \nendometriotic lesions. Traditional pharmacological and surgical \ntherapies (e.g. oral contraceptives, excision of endometriotic \nlesions) can be effective, but only temporarily. Recurrence is \noften high after cessation of contraceptives (and similar estrogen \nsuppressing medications) and even after surgery. Endometriotic \nlesions thrive when there is angiogenesis (like tumors and Mets) \ndue to their dependency on a enough blood supply. \nTherefore, anti-angiogenic compounds could potentially be \na viable treatment option. A current therapeutic approach to \npreventing angiogenesis, which is crucial in the development of \nendometriosis, is to pair an angiogenic cell (using a cell specific \nsurface molecule) with its killing agent. Hu analyzed tissue factor \nVII (VII-TF) as the cell specific surface molecule on angiogenic \nvascular endothelial cells (VEC). As discussed in Laschke & Menger, \nanti-angiogenic therapies are at a somewhat standstill due to the \nlack of specificity (i.e. anti-angiogenic target molecule). However, \nidentification of factor VII-TF on VECs has led to promising therapies \nsuch as, immunotherapy and photodynamic therapy [6].\nCardiovascular Health (e.g. Atherosclerosis)\nThere is a possible correlation between cardiovascular \ndisease (e.g. atherosclerosis) and endometriosis. Although the \npathophysiology of endometriosis remains somewhat unclear, \noxidative stress, and subsequent inflammation, may play a role. \nSystemic subclinical inflammation, possibly originating from \natherosclerosis, has been known to help characterize endometriosis. \nAs a result, studies have found that statins, due to their inhibitive \nand disruptive properties of certain enzymes and enzymatic \npathways, have potential to inhibit the growth of endometrial \nstromal cells. Because collagen contributes to the formation of scar \ntissue (fibrosis) associated with endometriosis, statins reduced the \ncontraction of and binding of endometrial stromal cells to collagen \nfibers. Furthermore, simvastatin was found to induce apoptosis of \nhuman endometrial stromal cells. High doses of statins, specifically \natorvastatin, were found to reduce endometrial implants and \nsubsequently inhibit angiogenesis. \nConclusion\nAlthough anti-angiogenics are a promising candidate for \nendometriosis treatment, it comes with complications. Since most \npatients affected by endometriosis are women of childbearing \nage, anti-angiogenic compounds need to be specialized towards \ninhibiting angiogenesis in endometriotic lesions and not in female \nstructures such as, the ovary, placenta and uterus. Accordingly, \nanti-angiogenic treatments can be teratogenic and impair fertility. \nFurthermore, even if the anti-angiogenic treatment can inhibit \na specific angiogenic growth factor, it may not be able to inhibit \nanother compensating angiogenic growth factor. Therefore, \nthese types of treatments may be effective towards the beginning \nstages of endometriosis or after surgical intervention by reducing \nrecurrence.\nIn addition to angiogenesis, another apparent comorbidity of \nendometriosis is cardiovascular disease, specifically atherosclerosis. \nAs discussed in Santoro atherosclerosis causes systemic subclinical \ninflammation that characterizes endometriosis. \nGibram found that statins, which are anti-inflammatories, have \nthe potential to not only treat atherosclerosis, but also inhibit the \ngrowth of endometrial stromal cells and angiogenesis. Therefore, \nstatins could be a possible treatment for endometriosis since they \nhave anti- inflammatory and antioxidant properties. In conclusion, \nalthough there were limited clinical trials and review papers \nobtained in the systematic search, there is promising potential \nof a relationship between endometriosis and vascular health. \nAs a result, new therapies for endometriosis are starting to be \ngeared toward treating vascularization (i.e. anti-angiogenics and \nanti-inflammatories). More clinical trials and studies need to be \nperformed in order to strengthen this relationship and its clinical \nimplications.\nReferences\n1. Gibran L, Maranhao R, Abrao M, Baracat E, Podgaec S (2014) Could \nstatins constitute a novel treatment for endometriosis? Systematic \nreview of the literature. European Journal of Obstetrics & Gynecology \nand Reproductive Biology 179: 153-158. \n\nCopyright@ Xia P | Biomed J Sci & Tech Res| BJSTR. MS.ID.002798.\nVolume 16- Issue 1\nDOI: 10.26717/BJSTR.2019.16.002798\n11781\nSubmission Link: https://biomedres.us/submit-manuscript.php\nAssets of Publishing with us\n• Global archiving of articles\n• Immediate, unrestricted online access\n• Rigorous Peer Review Process\n• Authors Retain Copyrights\n• Unique DOI for all articles\nhttps://biomedres.us/\nThis work is licensed under Creative\nCommons Attribution 4.0 License\nISSN: 2574-1241\nDOI: 10.26717/BJSTR.2019.16.002798\nXia P . Biomed J Sci & Tech Res\n2. Hu Z, Cheng J, Xu J, Ruf W, Lockwood C (2017) Tissue factor is an \nangiogenic-specific receptor for factor VII-targeted immunotherapy and \nphotodynamic therapy. Angiogenesis 20(1): 85-96. \n3. Laschke MW, Menger MD (2018) Basic mechanisms of vascularization \nin endometriosis and their clinical implications. Human Reproduction \nUpdate 24: 207-224. \n4. Laschke M, Menger M (2012) Anti-angiogenic treatment strategies for \nthe therapy of endometriosis. Human Reproduction Update 18(6): 682-\n702. \n5. Santoro L, D Onofrio F, Flore R, Gasbarrini A, Santoliquido A (2015) \nEndometriosis and atherosclerosis: what we already know and what \nwe have yet to discover. American Journal of Obstetrics and Gynecology \n213(3): 326-331. \n6. Soliman A, Yang H, Du E, Kelley C, Winkel C (2016) The direct and \nindirect costs associated with endometriosis: a systemic literature \nreview. Human Reproduction 31(4): 712-722.","source_license":"CC0","license_restricted":false}