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The metabolic role of pulmonary arterial fibroblasts in the activation of immune system during development of pulmonary arterial hypertension
Křivonosková, Monika ; Plecitá, Lydie (advisor) ; Zadražil, Zdeněk (referee)
The development of inflammation in the small distal pulmonary vessels plays an important role in the development of pulmonary arterial hypertension (PAH). One of the cell types found in the pulmonary vessels are fibroblasts, which, according to the "outside-in" theory, may be the first to respond to stimuli in the vessel, modulating remodeling of the pulmonary vessels toward the inner layers of the vessel and attracting other immune cells to the site. In addition to inflammation, the so- called Warburg effect also occurs in vessels affected by PAH, in which metabolism shifts toward glycolysis and lactate production. Among other changes, a pro-oxidative state is induced within the cell by mitochondrial metabolism and NADPH oxidase, leading to an imbalance in reactive oxygen species production. We therefore wanted to test whether calf lung fibroblasts with hypoxia-induced PAH have an active inflammasome, with which they would produce mature interleukin 1β (IL-1β) and to clarify the effect of a pro-oxidant environment on this expression. In our in vitro model we have confirmed IL-1β mRNA expression, but we were unable to detect its expression at the protein level. This was consistent with the inability to detect inflammasome activity. We believe that the inability to detect the protein form of IL-1β...
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The role of metabolism and immune system in pulmonary hypertension
Křivonosková, Monika ; Plecitá, Lydie (advisor) ; Vašek, Daniel (referee)
Pulmonary arterial hypertension is a low-incidence, fatal, disease that affects the pulmonary vessels, which remodel, thicken and gradually reduce lumen. During this signaling molecules are excreted from endothelial cells, which act vasoconstrictively and proliferatively on smooth muscle cells. There is also a reduction in the production of vaodilators, which again has a vasoconstrictive effect. Accumulation of immune cells in adventitia promotes smooth muscle cell proliferation, migration and differentiation of fibroblasts into myofibroblasts, which causes changes in the composition of the extracellular matrix. Changes in metabolism within all artery layers related to the transition to glycolysis and increased glucose uptake promote cell proliferation and modulate signaling leading to infiltration and activation of immune cells resulting in artery remodeling.
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