The purpose of this project is to obtain preliminary data over one year to explore the mechanism of the role of fat around vessels (PVAT) on microvascular dysfunction in HIV patients. The data will be used to develop an NIH R01 grant proposal to study microvascular function of PVAT signaling and the adipokine pathway in larger groups of HIV-positive patients.
Our previous experiments have detected impaired endothelial function of subdermal microvessels isolated from women with HIV who had with reduced nitric oxide (NO) activity and an increased reactive oxidative stress (ROS) compared to healthy control. PVAT enhanced normal endothelium derived relaxation (EDRs), but not to vessels (indicate a defective PVAT function from HIV patient. However, it is unknown the mechanism of PVAT during HIV infection contributes to the microvascular abnormality.
We hypothesized that microvascular endothelial dysfunction in HIV-positive patients is associated with disturbed adipokine signaling pathways (including leptin and adiponectin) in PVAT. This project will use human subcutaneous microvessels and PVAT as studying materials. This study will consist of two groups (n=6/group) of female subjects from The Women's Interagency HIV Study (WIHS) at DC site. Groups 1 will be young healthy controls and Group 2 will be young HIV infected patients with detectable viral load. Subjects with diabetes, hypertension or abnormalities in serum biochemical indexes will be excluded. As per previous IRB approved protocol, gluteal biopsy will be performed. This is an established procedure in our working group. We will: Aim1: to measure ROS and NO generation in micro vessels with PVAT (PVAT+) or without PVAT (PVAT -) to determine the role of PVAT on generation of ROS or NO in micro vessels; Aim2: to identify differential PVAT-derived adipokines from PVAT and plasma between two groups; Aim3: Measuring the different in RNA and microRNA gene array in PVAT to explore the possible molecular mechanism of PVAT.