MicroRNA Activation of LOX-1 Mechanisms in Endometriosis

Overview

Endometriosis is a disorder that occurs in women. With endometriosis, tissue that should be found in the womb is found in sites outside of the womb. This disorder impairs the function of the cells that line the body's blood vessels (endothelium). The endothelium helps to control blood flow in healthy vessels. Women with this disorder have an increased risk for high blood pressure and high cholesterol. They have a higher risk for cardiovascular disease, too. With this study, we will learn how endometriosis impairs the lining of blood vessels and increases the risk for disease.

Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk. Circulating factors, Low-density lipoprotein (LDL) and oxidized LDL (oxLDL), are two of many biomarkers of cardiovascular and inflammatory disease of endometriosis. An important signaling mechanism through which circulating LDL and oxLDL act is the lectin-like oxidized LDL receptor (LOX-1). LOX-1 signal transduction functionally results in pronounced endothelial dysfunction, a hallmark of CV. We hypothesis that one factor mediating the elevated risk of cardiovascular disease in endometriosis is microRNA (miRNA) activation of LOX-1 receptor mechanisms. Specific Aim 1. To test the hypothesis that LOX-1 receptor activation is increased leading to endothelial dysfunction in endometriosis. Specific Aim 2. To test the hypothesis that decreased microRNAs (i.e. let7-a, let7-b, let7-g, MiR98, Mi590-p) are driving increased LOX-1 receptor expression and function in endometriosis.

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