TitleSleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism.
Publication TypeJournal Article
Year of Publication2024
AuthorsBose K, Agrawal R, Sairam T, Mil J, Butler MP, Dhandapany PS
Date Published2024 Mar 15

Sleep fragmentation (SF) disrupts normal biological rhythms and has major impacts on cardiovascular health; however, it has never been shown to be a risk factor involved in the transition from cardiac hypertrophy to heart failure (HF). We now demonstrate devastating effects of SF on hypertrophic cardiomyopathy (HCM). We generated a transgenic mouse model harboring a patient-specific myosin binding protein C3 (MYBPC3) variant displaying HCM, and measured the progression of pathophysiology in the presence and absence of SF. SF induces mitochondrial damage, sarcomere disarray, and apoptosis in HCM mice; these changes result in a transition of hypertrophy to an HF phenotype by chiefly targeting redox metabolic pathways. Our findings for the first time show that SF is a risk factor for HF transition and have important implications in clinical settings where HCM patients with sleep disorders have worse prognosis, and strategic intervention with regularized sleep patterns might help such patients.

Alternate JournaliScience
PubMed ID38361607
PubMed Central IDPMC10867644
Grant List / WT_ / Wellcome Trust / United Kingdom
R01 NS102962 / NS / NINDS NIH HHS / United States