Inflammatory MicroRNAs and the Pathophysiology of Endometriosis and Atherosclerosis: Common Pathways and Future Directions Towards Elucidating the Relationship.

Abstract

Emerging data indicates an association between endometriosis and subclinical atherosclerosis, with women with endometriosis at a higher risk for cardiovascular disease later in life. Inflammation is proposed to play a central role in the pathophysiology of both diseases and elevated levels of systemic pro-inflammatory cytokines including macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) are well documented. However, a thorough understanding on the mediators and mechanisms which contribute to altered cytokine expression in both diseases remain poorly understood. MicroRNAs (miRNAs) are important post-transcriptional regulators of inflammatory pathways and numerous studies have reported altered circulating levels of miRNAs in both endometriosis and atherosclerosis. Potential contribution of miRNA-mediated inflammatory cascades common to the pathophysiology of both diseases has not been evaluated but could offer insight into common pathways and early manifestation relevant to both diseases which may help understand cause and effect. In this review, we discuss and summarize differentially expressed inflammatory circulating miRNAs in endometriosis subjects, compare this profile to that of circulating levels associated with atherosclerosis when possible, and then discuss mechanistic studies focusing on these miRNAs in relevant cell, tissue, and animal models. We conclude by discussing the potential utility of targeting the relevant miRNAs in the MIF-IL-6-TNF-α pathway as therapeutic options and offer insight into future studies which will help us better understand not only the role of these miRNAs in the pathophysiology of both endometriosis and atherosclerosis but also commonality between both diseases.