The Role Of Regulator Of G Protein Signaling 2 In Inflammatory Cytokine Release In Endotoxemia In Mice, Xin Tong Ma

Electronic Thesis and Dissertation Repository

In sepsis, lipopolysaccharide (LPS) activates toll-like receptor 4 to stimulate the release of inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNF-α), leading to cardiac dysfunction. Regulator of G protein signaling 2 (RGS2) limits G protein-coupled receptor signaling by increasing the rate of G protein deactivation or inhibiting G protein-effector interactions. We hypothesized that RGS2 deficiency would enhance proinflammatory responses in endotoxemia. Adult wild-type and RGS2^-/- C57BL/6 mice and neonatal cardiomyocytes were treated with LPS and assessed for inflammatory responses and cardiac function. Myocardial TNF-α expression was higher in RGS2^-/- mice during endotoxemia. Additionally, cardiac function was impaired in …

Cd4+ T-Cell Mediated Microvascular Endothelial Cell Death And Chronic Cardiac Allograft Rejection Involves Necroptosis, Cecilia Yt Kwok

Electronic Thesis and Dissertation Repository

Heart transplantation is the only viable option for patients with end-stage heart failure. Despite advances in immunosuppressive therapies, the rate of transplanted graft loss remains substantial. Graft loss is primarily due to tissue damage mediated by immune responses. Cell death and organ rejection can occur as an active molecular process through apoptotic and necrotic pathways. We now recognize that cell death may also ensue through a newly described form of programmed necrotic cell death, termed necroptosis that involves receptor-interacting protein kinase (RIPK) 1/3. In this study, I aim to establish the role of RIPK3 in T cell-mediated chronic cardiac allograft …

Methotrexate And Cardiovascular Events, Alpesh Shah

Electronic Thesis and Dissertation Repository

We conducted a systematic review and meta-analysis to assess the association of MTX with cardiovascular morbidity, cardiovascular mortality and all-cause mortality in patients with autoimmune disease. Our primary outcome was incident cardiovascular events. After screening 13,479 citations, we identified a total of 30 eligible studies. We synthesized adjusted risk estimates using a random effects model. MTX was significantly associated with a 25% reduction in cardiovascular events (pooled RR: 0.75, 95% CI: 0.65, 0.86, I²: 11%), a 55% reduction in cardiovascular mortality (0.45, 95% CI: 0.26, 0.80, I²: 33%) and a 40% reduction in all-cause mortality (0.60, …

Role Of Inos In Septic Pulmonary Microvascular Endothelial Cell Activation, Zahra Asad

Electronic Thesis and Dissertation Repository

Abstract

Background. Neutrophils and nitric oxide (NO) derived from inducible NO synthase (iNOS) contributes importantly to the pathophysiology of acute lung injury (ALI) and pulmonary microvascular endothelial cell (PMVEC) injury. However, the mechanism of neutrophil and neutrophil iNOS dependent PMVEC injury has not been addressed. In our studies, we assessed PMVEC activation under septic conditions, and defined the role of PMVEC vs. bone-marrow polymorphonuclear leukocytes (PMN) iNOS in this septic PMVEC activation.

Methods and Results. We isolated PMVEC from iNOS+/+ and iNOS-/- mice lungs magnetically by microbeads attached to anti-PECAM antibodies, sorted by flow cytometry (FACS) by DiI-acetylated low density …