Jiazi Chen
Pronouns: she/her/hers
Research Mentor(s): Salim Hayek
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine – Cardiology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors: Jiazi Chen, Pennelope Kunkle, Annika Tekumulla, Noor Sulaiman, Feriel Presswalla, Salim Hayek
Presenter: 29
Abstract
Cardiovascular disease (CVD) continues to be highly prevalent and remains the leading cause of death worldwide (WHO, 2022). While the specific mechanisms causing accelerated atherosclerosis are still under study, we suspect that soluble urokinase plasminogen activator receptor (suPAR) plays a significant role. suPAR is the cleaved form of uPAR, which has a physiological role in immune cell motility, and has increased release in response to proinflammatory cytokines (Thunø et al., 2009; Huai et al., 2006). Increased risk of CVD and atherosclerosis in human subjects has been observed with increased suPAR levels (Hayek et al., 2017). In addition, human subject data showed (1) high circulating levels of suPAR correlated with increased plaque numbers and (2) atherosclerosis was associated with increased suPAR levels (Thunø et al., 2009). From preliminary data, it has been shown that mouse models of atherosclerosis did not have increased suPAR levels. This indicates that atherosclerosis is not causing increased suPAR levels. To further investigate the pathogenic role of suPAR, we will inhibit uPAR interactions using a monoclonal antibody in a mouse model of atherosclerosis. To determine the most effective treatment schedule and dosage, we will give suPAR-tg mice IP injections of different dosages (mg/kg: 2, 5, 10, 20) of the antibody or 20mg/kg of IgG for a control mouse. Each mouse will have blood collected on days 0 (before treatment/control injection), 3, 7, and 14 alongside 200uL PBS injections. The serum will be obtained from centrifuged blood, plated into an enzyme-linked immunosorbent assay (ELISA), and levels of suPAR will be quantified using an optical density reading from a spectrophotometer. We will utilize the PCSK9 model (injecting a gain of function vector for PCSK9 into mice and placing mice on a Western diet) to rapidly induce atherosclerosis in mice for measurements of plaque size. We will use the most effective treatment schedule and dosage from toxicity trials in the mouse PCSK9 atherosclerosis model. We found a 20-30% decrease in blood suPAR levels of naive transgenic mice after antibody treatment and believe this decrease in suPAR by our monoclonal antibody treatment will result in decreased atherosclerotic plaque size in suPAR-tg mice with PCSK9 induced atherosclerosis. These results depict the effectiveness of anti-uPAR antibody injections in decreasing atherosclerosis severity by decreasing suPAR blood levels in mice. This indicates direction with future studies investigating anti-uPAR antibodies to combat atherosclerosis.
Biomedical Sciencs
