MicroRNA Activation of LOX-1 Mechanisms in Endometriosis

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.

Only women with endometriosis will complete this study. Once consented and screened, each subject is asked to take Atorvastatin (Lipitor, 10mg/day) for seven days. Participants will undergo experimental testing before and after the seven day intervention.

Oral atorvastatin (Lipitor) therapy (10mg/day) for seven days. Atorvastatin acts as a systemic LOX inhibitor.

Inclusion Criteria: Women between the ages of 18 and 45 years with endometriosis (diagnosis by prior laparoscopy by subject's own physician <5 years prior, and reported by the subject to the researchers) Exclusion Criteria: Use of nicotine-containing products (e.g. smoking, chewing tobacco, etc.) Diabetes (HbA1C .6.5%) BP>140/90 Taking pharmacotherapy that could alter peripheral vascular control (e.g. insulin sensitizing, cardiovascular medications) Pregnancy Breastfeeding Taking illicit and/or recreational drugs Abnormal liver function Rash, skin disease, disorders of pigmentation, known skin allergies Diagnosed or suspected metabolic or cardiovascular disease Persistent unexplained elevations of serum transaminases Known allergy to latex or investigative substances