Exploring the Link between Chronic Inflammation and Atherosclerosis-Endometriosis Association

Anastasia V. Poznyak ^1,*, Vasily N. Sukhorukov ², Igor A. Sobenin ², Vladimir P Ofitserov ³, Alexander L Golovyuk ⁴, Dmitriy Yu Serdyukov ⁵, Anton Y. Postnov ² , Alexander N. Orekhov ^2,*

Understanding shared inflammation mechanisms in atherosclerosis and endometriosis informs innovative interdisciplinary treatments, enhancing patient care and outcomes comprehensively.

Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) and endometriosis are both inflammatory diseases with significant implications for clinical practice and public health. Evidence Acquisition: To examine the clinical question regarding the relationship between ASCVD and endometriosis, we gathered data from various sources, including research studies and subsequent reference searches of retrieved articles. Our research strategies focused on identifying high-quality evidence through comprehensive study time periods and rigorous methods for quality assessment and article inclusion. Results: Our review of the literature reveals significant findings regarding the interplay between ASCVD and endometriosis. Both conditions share inflammation as a key factor in their pathophysiology. Inflammation not only contributes to the initiation and progression of vascular damage in ASCVD but also plays a role in the development and persistence of endometriosis. Women with endometriosis demonstrate higher levels of inflammatory markers and endothelial activation. Conclusions: Based on the available evidence, we conclude that there is a likely genetic link between ASCVD and the development of endometriosis. Additionally, the influence of estrogen on ASCVD varies depending on the stage of atherosclerosis. While estrogen may be protective in women with early artery blockages, it can pose a potential risk to those with established atherosclerosis. Clinicians should consider these factors when managing patients with ASCVD and endometriosis to optimize care.

Keywords: Atherosclerosis, Endometriosis, Inflammation.

References

Alessenko, A. V., Lebedev, ?. ?., & Kurochkin, I. N. (2018). Rol' sfingolipidov v serdechno-sosudistykh patologiiakh [The role of sphingolipids in cardiovascular pathologies]. Biomeditsinskaia khimiia, 64(6), 487–495. https://doi.org/10.18097/PBMC20186406487

Bjorkman, S., & Taylor, H. S. (2019). MicroRNAs in endometriosis: biological function and emerging biomarker candidates†. Biology of reproduction, 100(5), 1135–1146. https://doi.org/10.1093/biolre/ioz014

Blue, N. R., Murray-Krezan, C., Drake-Lavelle, S., Weinberg, D., Holbrook, B. D., Katukuri, V. R., Leeman, L., & Mozurkewich, E. L. (2018). Effect of ibuprofen vs acetaminophen on postpartum hypertension in preeclampsia with severe features: a double-masked, randomized controlled trial. American journal of obstetrics and gynecology, 218(6), 616.e1–616.e8. https://doi.org/10.1016/j.ajog.2018.02.016

Borodzicz, S., Czarzasta, K., Kuch, M., & Cudnoch-Jedrzejewska, A. (2015). Sphingolipids in cardiovascular diseases and metabolic disorders. Lipids in health and disease, 14, 55. https://doi.org/10.1186/s12944-015-0053-y

Chapron, C., Lafay-Pillet, M. C., Santulli, P., Bourdon, M., Maignien, C., Gaudet-Chardonnet, A., Maitrot-Mantelet, L., Borghese, B., & Marcellin, L. (2022). A new validated screening method for endometriosis diagnosis based on patient questionnaires. EClinicalMedicine, 44, 101263. https://doi.org/10.1016/j.eclinm.2021.101263

Chen, Z., Wang, C., Lin, C., Zhang, L., Zheng, H., Zhou, Y., Li, X., Li, C., Zhang, X., Yang, X., Guan, M., & Xi, Y. (2021). Lipidomic Alterations and PPARα Activation Induced by Resveratrol Lead to Reduction in Lesion Size in Endometriosis Models. Oxidative medicine and cellular longevity, 2021, 9979953. https://doi.org/10.1155/2021/9979953

Eldafira, E., Prasasty, V. D., Abinawanto, A., Syahfirdi, L., & Pujianto, D. A. (2021). Polymorphisms of Estrogen Receptor-α and Estrogen Receptor-β Genes and its Expression in Endometriosis. Turkish journal of pharmaceutical sciences, 18(1), 91–95. https://doi.org/10.4274/tjps.galenos.2019.94914

Farland, L. V., Degnan, W. J., Harris, H. R., Tobias, D. K., & Missmer, S. A. (2021). A prospective study of endometriosis and risk of type 2 diabetes. Diabetologia, 64(3), 552–560. https://doi.org/10.1007/s00125-020-05347-6

Goetz, T. G., Mamillapalli, R., & Taylor, H. S. (2016). Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice. Biology of reproduction, 95(6), 115. https://doi.org/10.1095/biolreprod.116.142877

Gruber, T. M., & Mechsner, S. (2021). Pathogenesis of Endometriosis: The Origin of Pain and Subfertility. Cells, 10(6), 1381. https://doi.org/10.3390/cells10061381

Guerriero, S., Conway, F., Pascual, M. A., Graupera, B., Ajossa, S., Neri, M., Musa, E., Pedrassani, M., & Alcazar, J. L. (2020). Ultrasonography and Atypical Sites of Endometriosis. Diagnostics (Basel, Switzerland), 10(6), 345. https://doi.org/10.3390/diagnostics10060345

Helbig, M., Vesper, A. S., Beyer, I., & Fehm, T. (2021). Does Nutrition Affect Endometriosis?. Geburtshilfe und Frauenheilkunde, 81(2), 191–199. https://doi.org/10.1055/a-1207-0557

Hogg, C., Horne, A. W., & Greaves, E. (2020). Endometriosis-Associated Macrophages: Origin, Phenotype, and Function. Frontiers in endocrinology, 11, 7. https://doi.org/10.3389/fendo.2020.00007

Iorga, A., Cunningham, C. M., Moazeni, S., Ruffenach, G., Umar, S., & Eghbali, M. (2017). The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biology of sex differences, 8(1), 33. https://doi.org/10.1186/s13293-017-0152-8

Kimber-Trojnar, Z., Dluski, D. F., Wierzchowska-Opoka, M., Ruszala, M., & Leszczynska-Gorzelak, B. (2022). Metformin as a Potential Treatment Option for Endometriosis. Cancers, 14(3), 577. https://doi.org/10.3390/cancers14030577

Kokot, I., Piwowar, A., Jedryka, M., Solkiewicz, K., & Kratz, E. M. (2021). Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis. International journal of molecular sciences, 22(5), 2295. https://doi.org/10.3390/ijms22052295

Laganà, A. S., Garzon, S., Götte, M., Viganò, P., Franchi, M., Ghezzi, F., & Martin, D. C. (2019). The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. International journal of molecular sciences, 20(22), 5615. https://doi.org/10.3390/ijms20225615

Lalami, I., Abo, C., Borghese, B., Chapron, C., & Vaiman, D. (2021). Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing. International journal of molecular sciences, 22(14), 7297. https://doi.org/10.3390/ijms22147297

Lee, Y. H., Tan, C. W., Venkatratnam, A., Tan, C. S., Cui, L., Loh, S. F., Griffith, L., Tannenbaum, S. R., & Chan, J. K. (2014). Dysregulated sphingolipid metabolism in endometriosis. The Journal of clinical endocrinology and metabolism, 99(10), E1913–E1921. https://doi.org/10.1210/jc.2014-1340

Leuzzi, C., Marzullo, R., & Modena, M. G. (2012). La menopausa è un fattore di rischio per la cardiopatia ischemica? [Is menopause a risk factor for ischemic heart disease in women?]. Giornale italiano di cardiologia (2006), 13(6), 401–406. https://doi.org/10.1714/1073.11757

Li, P. C., Yang, Y. C., Wang, J. H., Lin, S. Z., & Ding, D. C. (2021). Endometriosis Is Associated with an Increased Risk of Coronary Artery Disease in Asian Women. Journal of clinical medicine, 10(18), 4173. https://doi.org/10.3390/jcm10184173

Long, Q., Liu, X., Qi, Q., & Guo, S. W. (2016). Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor β2. Human reproduction (Oxford, England), 31(11), 2506–2519. https://doi.org/10.1093/humrep/dew237

Maas, A. H. E. M., Rosano, G., Cifkova, R., Chieffo, A., van Dijken, D., Hamoda, H., Kunadian, V., Laan, E., Lambrinoudaki, I., Maclaran, K., Panay, N., Stevenson, J. C., van Trotsenburg, M., & Collins, P. (2021). Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists. European heart journal, 42(10), 967–984. https://doi.org/10.1093/eurheartj/ehaa1044

Marchandot, B., Curtiaud, A., Matsushita, K., Trimaille, A., Host, A., Faller, E., Garbin, O., Akladios, C., Jesel, L., & Morel, O. (2022). Endometriosis and cardiovascular disease. European heart journal open, 2(1), oeac001. https://doi.org/10.1093/ehjopen/oeac001

Melo, A. S., Rosa-e-Silva, J. C., Rosa-e-Silva, A. C., Poli-Neto, O. B., Ferriani, R. A., & Vieira, C. S. (2010). Unfavorable lipid profile in women with endometriosis. Fertility and sterility, 93(7), 2433–2436. https://doi.org/10.1016/j.fertnstert.2009.08.043

Missmer, S. A., Tu, F. F., Agarwal, S. K., Chapron, C., Soliman, A. M., Chiuve, S., Eichner, S., Flores-Caldera, I., Horne, A. W., Kimball, A. B., Laufer, M. R., Leyland, N., Singh, S. S., Taylor, H. S., & As-Sanie, S. (2021). Impact of Endometriosis on Life-Course Potential: A Narrative Review. International journal of general medicine, 14, 9–25. https://doi.org/10.2147/IJGM.S261139

Mozos, I., Malainer, C., Horbanczuk, J., Gug, C., Stoian, D., Luca, C. T., & Atanasov, A. G. (2017). Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases. Frontiers in immunology, 8, 1058. https://doi.org/10.3389/fimmu.2017.01058

Mu, F., Rich-Edwards, J., Rimm, E. B., Spiegelman, D., & Missmer, S. A. (2016). Endometriosis and Risk of Coronary Heart Disease. Circulation. Cardiovascular quality and outcomes, 9(3), 257–264. https://doi.org/10.1161/CIRCOUTCOMES.115.002224

Mu, F., Rich-Edwards, J., Rimm, E. B., Spiegelman, D., Forman, J. P., & Missmer, S. A. (2017). Association Between Endometriosis and Hypercholesterolemia or Hypertension. Hypertension (Dallas, Tex. : 1979), 70(1), 59–65. https://doi.org/10.1161/HYPERTENSIONAHA.117.09056

Mu, F., Rich-Edwards, J., Rimm, E. B., Spiegelman, D., Forman, J. P., & Missmer, S. A. (2017). Association Between Endometriosis and Hypercholesterolemia or Hypertension. Hypertension (Dallas, Tex. : 1979), 70(1), 59–65. https://doi.org/10.1161/HYPERTENSIONAHA.117.09056

Muhaidat, N., Saleh, S., Fram, K., Nabhan, M., Almahallawi, N., Alryalat, S. A., Elfalah, M., & Elfalah, M. (2021). Prevalence of endometriosis in women undergoing laparoscopic surgery for various gynaecological indications at a Jordanian referral centre: gaining insight into the epidemiology of an important women's health problem. BMC women's health, 21(1), 381. https://doi.org/10.1186/s12905-021-01530-y

Okoth, K., Chandan, J. S., Marshall, T., Thangaratinam, S., Thomas, G. N., Nirantharakumar, K., & Adderley, N. J. (2020). Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. BMJ (Clinical research ed.), 371, m3502. https://doi.org/10.1136/bmj.m3502

Parasar, P., Ozcan, P., & Terry, K. L. (2017). Endometriosis: Epidemiology, Diagnosis and Clinical Management. Current obstetrics and gynecology reports, 6(1), 34–41. https://doi.org/10.1007/s13669-017-0187-1

Reslan, O. M., & Khalil, R. A. (2012). Vascular effects of estrogenic menopausal hormone therapy. Reviews on recent clinical trials, 7(1), 47–70. https://doi.org/10.2174/157488712799363253

Riazi, H., Tehranian, N., Ziaei, S., Mohammadi, E., Hajizadeh, E., & Montazeri, A. (2015). Clinical diagnosis of pelvic endometriosis: a scoping review. BMC women's health, 15, 39. https://doi.org/10.1186/s12905-015-0196-z

Rudzitis-Auth, J., Huwer, S. I., Scheuer, C., Menger, M. D., & Laschke, M. W. (2022). The ischemic time window of ectopic endometrial tissue crucially determines its ability to develop into endometriotic lesions. Scientific reports, 12(1), 5625. https://doi.org/10.1038/s41598-022-09577-z

Santanam, N., Song, M., Rong, R., Murphy, A. A., & Parthasarathy, S. (2002). Atherosclerosis, oxidation and endometriosis. Free radical research, 36(12), 1315–1321. https://doi.org/10.1080/1071576021000049908

Sanvicens, N., & Cotter, T. G. (2006). Ceramide is the key mediator of oxidative stress-induced apoptosis in retinal photoreceptor cells. Journal of neurochemistry, 98(5), 1432–1444. https://doi.org/10.1111/j.1471-4159.2006.03977.x

Smolarz, B., Szyllo, K., & Romanowicz, H. (2021). Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). International journal of molecular sciences, 22(19), 10554. https://doi.org/10.3390/ijms221910554

Tan, D. A., & Almaria, M. J. G. (2018). Postmenopausal endometriosis: drawing a clearer clinical picture. Climacteric : the journal of the International Menopause Society, 21(3), 249–255. https://doi.org/10.1080/13697137.2018.1450855

Taskin, O., Rikhraj, K., Tan, J., Sedlak, T., Rowe, T. C., & Bedaiwy, M. A. (2019). Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife. Journal of minimally invasive gynecology, 26(5), 781–784. https://doi.org/10.1016/j.jmig.2019.02.022

Taylor, H. S., Alderman Iii, M., D'Hooghe, T. M., Fazleabas, A. T., & Duleba, A. J. (2017). Effect of simvastatin on baboon endometriosis. Biology of reproduction, 97(1), 32–38. https://doi.org/10.1093/biolre/iox058

Thombre Kulkarni, M., Shafrir, A., Farland, L. V., Terry, K. L., Whitcomb, B. W., Eliassen, A. H., Bertone-Johnson, E. R., & Missmer, S. A. (2022). Association Between Laparoscopically Confirmed Endometriosis and Risk of Early Natural Menopause. JAMA network open, 5(1), e2144391. https://doi.org/10.1001/jamanetworkopen.2021.44391

Upson, K., & Missmer, S. A. (2020). Epidemiology of Adenomyosis. Seminars in reproductive medicine, 38(2-03), 89–107. https://doi.org/10.1055/s-0040-1718920

van Barneveld, E., Veth, V. B., Sampat, J. M., Schreurs, A. M. F., van Wely, M., Bosmans, J. E., de Bie, B., Jansen, F. W., Klinkert, E. R., Nap, A. W., Mol, B. W. J., Bongers, M. Y., Mijatovic, V., & Maas, J. W. M. (2020). SOMA-trial: surgery or medication for women with an endometrioma? Study protocol for a randomised controlled trial and cohort study. Human reproduction open, 2020(1), hoz046. https://doi.org/10.1093/hropen/hoz046

Vassilopoulou, L., Matalliotakis, M., Zervou, M. I., Matalliotaki, C., Krithinakis, K., Matalliotakis, I., Spandidos, D. A., & Goulielmos, G. N. (2019). Defining the genetic profile of endometriosis. Experimental and therapeutic medicine, 17(5), 3267–3281. https://doi.org/10.3892/etm.2019.7346

Verket, N. J., Falk, R. S., Qvigstad, E., Tanbo, T. G., & Sandvik, L. (2019). Development of a prediction model to aid primary care physicians in early identification of women at high risk of developing endometriosis: cross-sectional study. BMJ open, 9(12), e030346. https://doi.org/10.1136/bmjopen-2019-030346

Wilke, C. M., Bishop, K., Fox, D., & Zou, W. (2011). Deciphering the role of Th17 cells in human disease. Trends in immunology, 32(12), 603–611. https://doi.org/10.1016/j.it.2011.08.003

Xiao, F., Liu, X., & Guo, S. W. (2020). Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis. Frontiers in immunology, 11, 610963. https://doi.org/10.3389/fimmu.2020.610963

Zolbin, M. M., Mamillapalli, R., Nematian, S. E., Goetz, T. G., & Taylor, H. S. (2019). Adipocyte alterations in endometriosis: reduced numbers of stem cells and microRNA induced alterations in adipocyte metabolic gene expression. Reproductive biology and endocrinology : RB&E, 17(1), 36. https://doi.org/10.1186/s12958-019-0480-0