Association of Inflammatory Markers/Cytokines with Cardiovascular Risk Manifestation in Patients with Endometriosis

Abstract

This study is aimed at determining the association of inflammatory markers and proinflammatory cytokines with cardiovascular risk manifestation in women with endometriosis as compared to healthy controls. A total of 181 females of reproductive age with the absence of other inflammatory or autoimmune disorders and a lack of hormonal therapy for at least 6 months voluntarily participated in this investigation. Patients were 81 females, laparoscopically diagnosed with endometriosis, while the control group comprised 80 healthy females without any pelvic pathology. All subjects were 20-40 years of age. Exclusion criteria were diabetes, obesity, hypertension, metabolic diseases, cardiovascular, and renal disorders. C-reactive protein, fibrinogen, homocysteine, interleukin-17, and interleukin-33 were analyzed using commercially available ELISA kits. For statistical interpretation, the unpaired Student “ t ” test was used. All inflammatory markers and cytokines demonstrated elevated levels ( P < 0.001 ) in endometriosis patients as compared to healthy controls. The results of the study revealed that the patients with endometriosis demonstrate a hypercoagulable status due to inflammation, which initiates atherosclerosis and associated complications. Hence, endometriosis can cause a risk of cardiovascular disorders in these patients.

IL-17: an important pathogenic factor in endometriosis

“…They speculated that this result could be due to the fact that the inflammatory response seems to be low at more severe stages of endometriosis, just as Salmeri et al suggested 75 . Besides, some other reports even demonstrated that in the context of endometriosis, IL-17A was elevated in the plasma 76 and PF of women with endometriosis compared to controls and that endometriotic lesions produce IL-17A 42 , 60 . Sabbaghi et al declared that a similar elevation in IL-17A level was observed both in blood serum and follicular fluid (FF) when endometriosis and infertility co-exist 77 .…”

Association of endometriosis with cardiovascular disease: Genetic aspects (Review)

“…Previous findings have suggested an association between endometriosis and an increased risk of developing CVD in various populations ( 15 , 17 - 23 ), with this observation posing the interesting question regarding the potential role of a shared genetic background on the co-occurrence of endometriosis and CVD. Considering that various genes involved in inflammation are significantly associated with both endometriosis and CVD, it appears reasonable that shared genetic components between these diseases exist.…”

“…Women with endometriosis, which is a heterogeneous condition, are at a high risk of developing several other chronic diseases, including cancer ( 11 ) and various autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis, rheumatoid arthritis (RA), Crohn's disease, scleroderma, ulcerative colitis, autoimmune thyroid disorder, Sjögren's syndrome, coeliac disease and ankylosing spondylitis ( 12 - 14 ). Of note, previous findings have suggested that endometriosis can increase the susceptibility for cardiovascular disorders in these women, considering that both conditions share pathogenic mechanisms based on hormonal deviations, as well as aberrant immunology and genetic profiles ( 15 - 17 ). Moreover, studies have reported a similar potential association between endometriosis and atherosclerotic CVD, underlying similar pathogenic mechanisms including coronary microvascular dysfunction, endothelial dysfunction and atherogenic lipid profile ( 18 , 19 ).…”

“…Additionally, the deregulation of the inflammasome pathway has been suggested to participate in disease progression through promoting adhesion, invasion and cell proliferation and by preventing cell death ( 78 ). In a recent study by Rafi et al ( 17 ), it was shown that in women with endometriosis, inflammation causes a hypercoagulable status, which leads to the development of atherosclerosis and other cardiac complications. Thus, it can be hypothesized that endometriosis may be a risk factor of cardiovascular disorders in these patients.…”

Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS

“…Moreover, epidemiological data indicate that endometriosis patients present an increased risk for cardiovascular disease (CVD) [ 4 ], including major cardiovascular events [ 5 ]. This is partly explained by the hormonal treatments or hysterectomy/oophorectomy [ 5 ], but endometriosis-associated conditions such as chronic systemic inflammation [ 6 ] and imbalance between oxidative species and anti-oxidative defenses (oxidative stress) [ 7 ] also independently contribute to CVD onset and progression [ 8 ]. Independently of the hormonal treatments, endometriosis patients present a hypercoagulable status that, whilst supporting the healing of the endometriotic lesions, contributes to the occurrence of thrombo-embolic events and tissue fibrosis [ 9 ].…”