Abstract Background Low selenium status is clinically associated with poor cardiovascular outcomes. It has even been reported to cause an endemic cardiomyopathy in a specific region with low soil selenium levels. Yet, how selenium deficiency triggers myocardial dysfunction remains insufficiently defined. Purpose To determine whether dietary selenium deficiency directly impairs myocardial performance and to identify molecular pathways linking systemic selenium depletion to cardiac function. Methods C57BL/6N mice were exposed to a selenium-controlled diet, deficient (0 ppm) versus sufficient (0.15 ppm), for 12 weeks to induce a reproducible deficiency state. Cardiac morphology and function were evaluated longitudinally by echocardiography, including deformation-based indices sensitive to subclinical systolic impairment. Transcriptomic profiling by RNA sequencing of cardiac left ventricular and spleen tissues was performed to delineate selenium-responsive pathways, followed by targeted validation of selected transcripts using quantitative PCR and western blot. Results Despite preserved global pump performance (ejection fraction) and absence of overt chamber enlargement, selenium-deficient mice exhibited early impairment in global longitudinal strain (GLS) analyses and increase of markers of cardiac wall stress (Nppb and Nppa). RNA sequencing revealed coordinated modulation of pathways governing redox balance, mitochondrial stress responses, contractile apparatus organization and early hypertrophic signaling. Strikingly, core circadian pathways were prominently affected, indicating that selenium deficiency perturbs redox–clock regulatory networks. Parallel redox-clock signatures in spleen tissue suggested a systemic rather than isolated myocardial adaptation. Additional sex-stratified analyses indicated differential vulnerability to selenium depletion, with the male sex demonstrating more pronounced cardiac functional and transcriptional changes. Conclusions Dietary selenium deficiency initiates subclinical myocardial dysfunction accompanied by integrated redox, mitochondrial and circadian signatures across cardiac and immune tissues. These findings identify selenium as a modifiable regulator of early heart failure trajectories and highlight redox–circadian networks as potential mechanistic targets.For image description, please refer to the figure legend and surrounding text.
Guo et al. (Fri,) studied this question.