Prolyl 4-hydroxylases as therapeutic targets. HIF and collagen prolyl 4-hydroxylases in hypertrophic cardiac disease and pulmonary fibrosis, respectively.
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Leena Palotie Auditorium 101A, Aapistie 5A
Topic of the dissertation
Prolyl 4-hydroxylases as therapeutic targets. HIF and collagen prolyl 4-hydroxylases in hypertrophic cardiac disease and pulmonary fibrosis, respectively.
Doctoral candidate
Licentiate of medicine Tapio Röning
Faculty and unit
University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, ECM and Hypoxia
Subject of study
Biochemistry and molecular medicine
Opponent
Professor Dörthe Katschinski, University Medical Center Göttingen
Custos
Professor Peppi Karppinen, University of Oulu
Enzymes that have a central effect on the hypoxia response and collagen formation – prolyl 4-hydroxylases as therapeutic targets
Heart and lung diseases are serious and a major cause of mortality. The goal of the dissertation was to find new ways to influence these diseases. The body's response, which is activated in low oxygen concentration, affects metabolism and many other systems in the body.
In this dissertation, we investigated how activation of body’s response to low oxygen amount i.e. hypoxia affects the aging heart. The study showed that modest activation of this response protects the heart from aging-related hypertrophy. The research was done using an experimental animal model. In this model, the hypoxia response is genetically activated by reducing the amount of HIF prolyl 4-hydroxylase, which acts as the body's oxygen sensor.
Idiopathic pulmonary fibrosis is a serious/progressive lung disease with limited treatment options. The formation of excess connective tissue and the deterioration of lung function are central to the development of the disease. A large part of the connective tissue formed in the disease is collagen. In the dissertation, it was shown that silencing collagen prolyl 4-hydroxylases reduces the accumulation of collagen in the lungs. This study was done using an experimental animal model that mimics idiopathic pulmonary fibrosis. In addition, new digital methods were developed, that can be utilized in the microscopic examination of pulmonary fibrosis.
In this dissertation, we investigated how activation of body’s response to low oxygen amount i.e. hypoxia affects the aging heart. The study showed that modest activation of this response protects the heart from aging-related hypertrophy. The research was done using an experimental animal model. In this model, the hypoxia response is genetically activated by reducing the amount of HIF prolyl 4-hydroxylase, which acts as the body's oxygen sensor.
Idiopathic pulmonary fibrosis is a serious/progressive lung disease with limited treatment options. The formation of excess connective tissue and the deterioration of lung function are central to the development of the disease. A large part of the connective tissue formed in the disease is collagen. In the dissertation, it was shown that silencing collagen prolyl 4-hydroxylases reduces the accumulation of collagen in the lungs. This study was done using an experimental animal model that mimics idiopathic pulmonary fibrosis. In addition, new digital methods were developed, that can be utilized in the microscopic examination of pulmonary fibrosis.
Last updated: 23.1.2024