Cyanotic (hypoxemic) congenital heart defects (CHD) account for approximately a quarter of all CHD and prove to be a negative prognostic factor for long-term mortality and morbidity. Evidence exists regarding sex differences in the incidence of CHD at birth and in the risk of major cardiac outcomes in adult patients with CHD. Understanding the etiology of CHD is thus essential for the development of new treatment strategies for pediatric and adult CHD patients.
CHD etiologies can be categorized as genetic or non-genetic. Environmental (non-genetic) risk factors include diabetes, obesity, and hypoxic states. Hypoxemia resulting from cyanotic CHD is one of the most common insults in early postnatal development. Evidence from human and animal studies demonstrates a clear link between adverse fetal and perinatal conditions, such as hypoxia, and an increased risk of cardiovascular disease later in life.
Recent findings highlight the role of epitranscriptomic (RNA epigenetic) mechanisms in heart development and disease. These modifications may be influenced by oxygen availability. This project examines the relationship between epitranscriptomic regulation, perinatal hypoxia, and HIF-1α, a key hypoxia-response factor, in CHD patient samples and samples from an experimental model, with a focus on sex-based differences.
Supported by the Czech Science Foundation (project no. 24-10497S 2024-2026; PI: Marketa Hlavackova, PhD, IPHYS; collaboration with Prof. J. Janousek, the Children´s Heart Centre of 2nd Faculty of Medicine, Charles University and University Hospital Motol and G. Pavlinkova, PhD, Institute of Biotechnology of the Czech Academy of Sciences).
