Hypoxia in cardiometabolic and retinal health. Hemoglobin levels and retinal HIF-P4H-2 inhibition as emerging treatment strategies
Thesis event information
Date and time of the thesis defence
Topic of the dissertation
Hypoxia in cardiometabolic and retinal health. Hemoglobin levels and retinal HIF-P4H-2 inhibition as emerging treatment strategies
Doctoral candidate
Licentiate of Medicine Samuli Sakko
Faculty and unit
University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, ECM & Hypoxia
Subject of study
Biochemistry and Molecular Medicine
Opponent
Professor Kai Kaarniranta, University of Eastern Finland
Custos
Professor Peppi Karppinen, University of Oulu
Hypoxia in cardiometabolic and retinal health. Hemoglobin levels and retinal HIF-P4H-2 inhibition as emerging treatment strategies
Oxygen is a fundamental requirement for life, and the body reacts quickly to changes in its availability. Low oxygen levels, hypoxia, are associated with cardiovascular diseases in the aging population, whereas high oxygen levels, hyperoxia, predispose premature infants to blinding retinal disease. Hemoglobin (Hb) transports oxygen in the bloodstream, and its concentration affects how much oxygen tissues receive. At the cellular level, changes in oxygen levels are sensed by hypoxia inducible factor (HIF), which regulates oxygen consumption and transport through its target genes. The activity of HIF is controlled by oxygen sensing HIF-prolyl 4-hydroxylase enzymes (HIF-P4H).
In our study, we examined Hb levels within the Finnish reference range as an indicator of tissue oxygenation. High Hb levels were associated with unfavorable heart rate variability and larger retinal venous diameter in middle aged individuals. In addition, high Hb levels were consistently linked to several cardiovascular and metabolic risk factors: obesity, elevated blood glucose, an unfavorable lipid profile, and higher blood pressure, both in middle aged adults and already in adolescence.
In the second part of the study, we used an animal model with a partially inactive HIF-P4H-2 enzyme, resulting in a continuously active HIF response. HIF-P4H-2 was widely expressed in the retina, and its partial deficiency did not appear to cause harm. Partial deficiency of HIF-P4H-2 protected the retina from vascular degeneration and from the formation of poor quality new blood vessels in an animal model of retinopathy of prematurity.
The results show that low Hb levels within the reference range appear to be associated with better cardiovascular and metabolic health starting already in adolescence, reinforcing previously observed findings. HIF-P4H-2 is a promising target for drug development for preventing retinopathy of prematurity.
In our study, we examined Hb levels within the Finnish reference range as an indicator of tissue oxygenation. High Hb levels were associated with unfavorable heart rate variability and larger retinal venous diameter in middle aged individuals. In addition, high Hb levels were consistently linked to several cardiovascular and metabolic risk factors: obesity, elevated blood glucose, an unfavorable lipid profile, and higher blood pressure, both in middle aged adults and already in adolescence.
In the second part of the study, we used an animal model with a partially inactive HIF-P4H-2 enzyme, resulting in a continuously active HIF response. HIF-P4H-2 was widely expressed in the retina, and its partial deficiency did not appear to cause harm. Partial deficiency of HIF-P4H-2 protected the retina from vascular degeneration and from the formation of poor quality new blood vessels in an animal model of retinopathy of prematurity.
The results show that low Hb levels within the reference range appear to be associated with better cardiovascular and metabolic health starting already in adolescence, reinforcing previously observed findings. HIF-P4H-2 is a promising target for drug development for preventing retinopathy of prematurity.
Created 16.5.2026 | Updated 18.5.2026