Hypoxia-inducible factor 1 (Hif-1) is the master regulator of transcriptional responses of cells to decreased oxygen availability. Research teams of the Institutes of Biotechnology and Physiology CAS and the 1st Medical Faculty UK showed that genetic mutation of the Hif-1a gene suppresses the embryonic development of preganglionic and postganglionic neurons of the sympathetic nerve system and negatively affects sympathetic innervation of the heart that plays a primary role in the regulation of heart rate and contractility. Mice with conditional deletion of Hif-1a gene exhibited coronary artery anomalies and decreased cardiac contractile function. These data indicate that deregulation of the transcription factor Hif-1a can result in serious cardiovascular diseases associated with the autonomic nervous system dysbalance and open the way to a development of new therapeutic strategies.
Impaired sympathetic innervation of hearts with Hif-1a deletion (Hif1aCKO): Immunohistochemical staining of tyrosine hydroxylase (TH) in posterior view of hearts, and quantification of TH-positive fibers per ventricle area in E16.5 control and Hif1aCKO littermates.
Bohuslavová, Romana - Čerychová, Radka - Papoušek, František - Olejníčková, Veronika - Bartoš, M. - Goerlach, A. - Kolář, František - Sedmera, David - Semenza, G.L. - Pavlínková, Gabriela: HIF-1 alpha is required for development of the sympathetic nervous system. Proceedings of the National Academy of Sciences of the United States of America. Roč. 116, č. 27 (2019), s. 13414-13423. ISSN 0027-8424, IF: 9.580, 2018. DOI: 10.1073/pnas.1903510116