Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions

Nenicu, Anca; Gu, Yuan; Körbel, Christina; Menger, Michael D.; Laschke, Matthias W.

doi:10.1111/bph.13874

Cited by 17 publications

(8 citation statements)

References 54 publications

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“…This observation is in line with previous studies reporting that parecoxib not only inhibits the activity of COX-2 but also suppresses the expression of the enzyme. 38,39 In the initial phase of engraftment, ectopic endometrial tissue is particularly dependent on the rapid establishment of a functional microvasculature to guarantee a sufficient oxygen and nutrient supply, 40,41 which is a major prerequisite for cell survival and proliferative activity. However, the early vascularization of the lesions was impaired in parecoxib-treated animals, as indicated by a significantly lower microvessel density at day 7 when compared with vehicle-treated controls.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cyclooxygenase-2 Suppresses the Recruitment of Endothelial Progenitor Cells in the Microvasculature of Endometriotic Lesions

Rudzitis‐Auth

Nickels

Menger

et al. 2018

The American Journal of Pathology

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The incorporation of endothelial progenitor cells (EPCs) into newly developing blood vessels contributes to the vascularization of endometriotic lesions. We analyzed whether cyclooxygenase (COX)-2 signaling regulates this vasculogenic process. Endometriotic lesions were surgically induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN [Tie2/green fluorescent protein (GFP)] 287 Sato mice. The animals received β-estradiol 17-valerate once a week and were treated daily with the selective COX-2 inhibitor parecoxib (25 mg/kg) or vehicle (control) for 7 and 28 days. Analyses involved the determination of lesion growth, cyst formation, homing of GFP/Tie2 EPCs, numbers of circulating EPCs, vascularization, cell proliferation, apoptosis, and immune cell infiltration by means of high-resolution ultrasonography, caliper measurements, flow cytometry, histologic analysis, and immunohistochemical analysis. In parecoxib-treated mice, blood circulating EPCs were higher, but numbers of recruited EPCs in endometriotic lesions were significantly lower when compared with controls. This finding was associated with an impaired early vascularization and stromal tissue growth as well as reduced glandular secretory activity of the lesions. Parecoxib-treated lesions further contained less proliferating and more apoptotic cells and exhibited lower numbers of infiltrating macrophages and neutrophilic granulocytes. These findings demonstrate that the inhibition of COX-2 suppresses vasculogenesis in endometriotic lesions, which may contribute to an impaired lesion vascularization and growth.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Cyclooxygenase-2 Suppresses the Recruitment of Endothelial Progenitor Cells in the Microvasculature of Endometriotic Lesions

Rudzitis‐Auth

Nickels

Menger

et al. 2018

The American Journal of Pathology

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“…However, the endometriosis pathogenesis has not been cleared, although retrograde menstruation has recently become an extensively accepted theory. During menstruation, endometrial tissue in the menstrual blood flows back through the fallopian tube and into the ovary or peritoneal cavity, thereby adhering to other tissues and growing [ 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

et al. 2020

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Endometriosis is common in reproductive-age women and its pathology is to increase proliferation and migration to enhance epithelial-to-mesenchymal transition progression (EMT). However, treatments are currently limited, so it is important to explore new therapeutic drugs. Hence, in this study, we investigate the therapeutic effect of fucoidan (FC) on the progression and mechanisms of endometriosis. The cell viability of endometrial cell lines End1/E6E7 and Vk2/E6E7 treated with different concentrations of FC were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting. Cell migration was evaluated using wound-healing assay. In an in vivo experiment, female Balb/c mice received surgically induced endometriosis followed by different concentrations of fucoidan for 6 weeks. High-frequency ultrasound imaging was applied to detect subsequent lesion growth. The results demonstrated that fucoidan inhibited the viability and migration ability of End1/E6E7 and Vk2/E6E7 cells. Additionally, the administration of fucoidan reduced the volume and weight of endometriotic lesions, decreased inflammatory cytokines and vascular endothelial growth factor (VEGF) of serum and lesions, and improved EMT proliferation and apoptosis-related protein expression. For the first time, fucoidan indicated anti-proliferative and anti-inflammatory effects as well as inhibited EMT progression and induced apoptosis, improving endometriosis.

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“… 127 Similarly, telmisartan inhibited vascularization, immune cell content, and growth of murine endometriosis-like lesions. 128 , 129 …”

Section: Endometriosis and Cardiovascular Pharmacologymentioning

confidence: 99%

Endometriosis and cardiovascular disease

Marchandot

Curtiaud

Matsushita

et al. 2022

European Heart Journal Open

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Endometriosis is a chronic gynecological disease affecting one in ten reproductive-age women. It is defined as the presence of endometrium-like tissue outside the uterus. Beyond this placid anatomical definition, endometriosis is a complex, hormonal, inflammatory, and systemic condition that poses significant familial, psychological, and economic burden. The interaction between the cardiovascular system and endometriosis has become a field of interest as the underlying mutual mechanisms become better understood. On the basis of accumulating fundamental and clinical evidence, it is likely that there exists a close relationship between endometriosis and the cardiovascular system. Therefore, investigating the endometriosis– cardiovascular interaction is highly clinically significant. In this Review, we highlight our current understanding of the pathophysiology of endometriosis with systemic hormonal, proinflammatory, pro-angiogenic, immunologic, and genetic processes beyond the peritoneal microenvironment. Additionally, we provide current clinical evidence about how endometriosis interact with cardiovascular risk factors and cardiovascular disease. To date, only small associations between endometriosis and cardiovascular disease have been reported in observational studies, inherently limited by the potential influence of unmeasured confounding. Cardiovascular disease in women with endometriosis remains understudied, under-recognized and underdiagnosed. More detailed study of the cardiovascular-endometriosis interaction is needed to fully understand its clinical relevance, underlying pathophysiology, possible means of early diagnosis and prevention.

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Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions

Abstract: Combination therapy with telmisartan and a COX-2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis.

Cited by 17 publications

References 54 publications

Inhibition of Cyclooxygenase-2 Suppresses the Recruitment of Endothelial Progenitor Cells in the Microvasculature of Endometriotic Lesions

Inhibition of Cyclooxygenase-2 Suppresses the Recruitment of Endothelial Progenitor Cells in the Microvasculature of Endometriotic Lesions

The Potential Effect of Fucoidan on Inhibiting Epithelial-to-Mesenchymal Transition, Proliferation, and Increase in Apoptosis for Endometriosis Treatment: In Vivo and In Vitro Study

Endometriosis and cardiovascular disease

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