Atherosclerosis is a disease defined as the accumulation of lipids with the arterial intima. Systemic lupus erythematosus (SLE), an autoimmune disorder, is characterized by the production of anti-nuclear antibodies. Patients suffering from SLE also have an increased risk for premature atherosclerosis. Most disturbing are studies showing that premenopausal women are 50 times more likely to develop fatal myocardial infarction compared to normal premenopausal women. The link between the two diseases has not been extensively studied, however it is thought that immune dysregulation plays a role in the acceleration of atherosclerosis in SLE. The long term goal of this project is to understand the mechanism of autoimmune-mediated accelerated atherosclerosis, specifically the role of T cells in mediating disease. In the first aim, we will determine the immune components necessary to accelerate atherosclerosis. In order to accomplish this, we will use a mouse model of lupus-accelerated atherosclerosis to determine the lupus susceptibility loci necessary to accelerate atherosclerosis. We will also adoptive transfer and immune cell depletion techniques to determine the cellular types needed to mediate changes in vascular disease in the presence of SLE. The goal of the second aim is to determine if T cells bias toward a pathogenic T helper 17 response in SLE leads to enhanced vascular disease. In this aim we will investigate the molecular mechanism of T helper 17 and induced regulatory T cell differentiation in the B6.Sle1.2.3 mouse model. Ultimately, these studies will enhance our knowledge of both vascular disease and lupus.

Public Health Relevance

Patients with SLE, especially premenopausal women, have an increased risk for developing cardiovascular disease. Additionally, many treatments for SLE disease are thought to exacerbate vascular complications. Therefore understanding the mechanism autoimmune-accelerated atherosclerosis is necessary for the development of new therapeutic targets to treat both autoimmune and vascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HL105024-02
Application #
8197980
Study Section
Special Emphasis Panel (ZRG1-CVRS-S (29))
Program Officer
Meadows, Tawanna
Project Start
2010-12-01
Project End
2012-02-29
Budget Start
2011-12-01
Budget End
2012-02-29
Support Year
2
Fiscal Year
2012
Total Cost
$10,035
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pathology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212