MicroRNA Activation of LOX-1 Mechanisms in Endometriosis

Phase 4

Terminated

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in Nitric Oxide Dependent Vasodilation in the Skin	before and after intervention (7 days)	area under the curve of laser Doppler flux/mean arterial pressure \* log acetylcholine (mol/L)

Secondary Outcome Measures