Dysregulation of hypoxia-inducible factor 1 alpha in the sympathetic nervous system accelerates diabetic cardiomyopathy

0571541 - BTÚ 2024 RIV GB eng J - Journal Article
Hrabalová, Petra - Bohuslavová, Romana - Matějková, Kateřina - Papoušek, František - Sedmera, David - Abaffy, Pavel - Kolář, František - Pavlínková, Gabriela
Dysregulation of hypoxia-inducible factor 1 alpha in the sympathetic nervous system accelerates diabetic cardiomyopathy.
Cardiovascular Diabetology. Roč. 22, č. 1 (2023), č. článku 88. E-ISSN 1475-2840
R&D Projects: GA MŠMT(CZ) LX22NPO5104; GA ČR(CZ) GA21-03847S; GA MŠMT(CZ) EF18_046/0016045
Research Infrastructure: CCP II - 90126; Czech-BioImaging II - 90129
Institutional support: RVO:86652036 ; RVO:67985823
Keywords : Cardiac function * Inflammation * Diabetic cardiomyopathy * Collagen deposition * Sympathetic neurons
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 9.3, year: 2022
Method of publishing: Open access
https://cardiab.biomedcentral.com/articles/10.1186/s12933-023-01824-5

BackgroundAn altered sympathetic nervous system is implicated in many cardiac pathologies, ranging from sudden infant death syndrome to common diseases of adulthood such as hypertension, myocardial ischemia, cardiac arrhythmias, myocardial infarction, and heart failure. Although the mechanisms responsible for disruption of this well-organized system are the subject of intensive investigations, the exact processes controlling the cardiac sympathetic nervous system are still not fully understood. A conditional knockout of the Hif1a gene was reported to affect the development of sympathetic ganglia and sympathetic innervation of the heart. This study characterized how the combination of HIF-1 alpha deficiency and streptozotocin (STZ)-induced diabetes affects the cardiac sympathetic nervous system and heart function of adult animals.MethodsMolecular characteristics of Hif1a deficient sympathetic neurons were identified by RNA sequencing. Diabetes was induced in Hif1a knockout and control mice by low doses of STZ treatment. Heart function was assessed by echocardiography. Mechanisms involved in adverse structural remodeling of the myocardium, i.e. advanced glycation end products, fibrosis, cell death, and inflammation, was assessed by immunohistological analyses.ResultsWe demonstrated that the deletion of Hif1a alters the transcriptome of sympathetic neurons, and that diabetic mice with the Hif1a-deficient sympathetic system have significant systolic dysfunction, worsened cardiac sympathetic innervation, and structural remodeling of the myocardium.ConclusionsWe provide evidence that the combination of diabetes and the Hif1a deficient sympathetic nervous system results in compromised cardiac performance and accelerated adverse myocardial remodeling, associated with the progression of diabetic cardiomyopathy.
Permanent Link: https://hdl.handle.net/11104/0345902