Life Sciences Commons^™

The Role Of Adaptive Immunity In Chronic Hypoxia-Induced Pulmonary Hypertension, Levi David Maston

Biomedical Sciences ETDs

Inflammation is a prominent pathologic feature in pulmonary arterial hypertension as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension (PH) caused by chronic hypoxia (CH). Inflammatory cells, through various mechanisms, have the capability to increase pulmonary vascular resistance in various disease states. CD4⁺T cells have the potential to play a significant role in the disease process initiated by hypoxia. CD4⁺T cells are largely responsible for orchestrating downstream immune processes and are critical in focusing and amplifying …

Role Of Pkcbeta And Oxidant Signaling In Neonatal Pulmonary Hypertension, Joshua R. Sheak

Biomedical Sciences ETDs

Chronic hypoxia (CH)-induced vasoconstriction has been implicated in the pathogenesis of pulmonary hypertension (pHTN) in infants with chronic cardiorespiratory disorders. Although endothelial dysfunction, reduced nitric oxide (NO) bioavailability and oxidative stress contribute to a variety of cardiovascular disorders, their contribution to enhanced vasoconstrictor reactivity in neonatal pHTN is poorly understood. We therefore hypothesized that neonatal CH augments pulmonary vasoconstrictor reactivity by limiting NO-dependent pulmonary vasodilation and by promoting the generation of reactive oxygen species (ROS).

Enzymatic sources of ROS in the vasculature include NADPH oxidase isoforms, xanthine oxidase, and uncoupled endothelial nitric oxide synthase (eNOS). The mitochondria are also a …

Autophagy Is Stimulated By Acute High Intensity Interval Exercise In Human Skeletal Muscle And Electrical Pulse Stimulation In C2c12 Myotubes In Vitro, Kurt A. Escobar

Health, Exercise, and Sports Sciences ETDs

Purpose: 1) To compare the effects of an acute bout of HIIT exercise (treadmill running) on autophagy to MICT exercise in human skeletal muscle 3 hours post exercise, and 2) to test an in vitro model of muscle contraction-induced autophagy using electrical pulse stimulation in C2C12 myotubes. Methods: Study 1: Ten recreationally active males and females completed a bout of high intensity interval training (HIIT) exercise and moderate intensity continuous exercise (MICT) exercise in a fasted state. Muscle biopsies from the vastus lateralis were taken pre and 3 hours post-exercise. Muscle tissue was analyzed for protein expression of markers of …

Cholesterol Regulation Of Pulmonary Endothelial Calcium Entry Following Chronic Hypoxia, Bojun Zhang

Biomedical Sciences ETDs

Chronic hypoxia (CH)-induced pulmonary hypertension (PH) is associated with diminished ATP-induced endothelial Ca2+ entry as well as membrane cholesterol in pulmonary arteries. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. Because endothelium-dependent vasodilation is closely associated with pulmonary endothelial [Ca2+]i, the blunted agonist-induced Ca2+ influx in pulmonary artery endothelial cells (PAEC) may contribute to the development of CH-induced PH. Interestingly, impaired agonist-induced Ca2+ influx in PAEC following CH can be restored by membrane cholesterol supplementation. In the current studies, we hypothesized that impaired Ca2+ entry in …