Type 1 Diabetes Differentially Disrupts Right and Left Ventricular Daily Rhythms

Circadian rhythms are endogenous ∼24-hour cycles that regulate cardiovascular physiology. While circadian regulation of the left ventricle (LV) is well established, whether the right ventricle (RV) exhibits intrinsic rhythmicity is not known. Here, we provide the first evidence that the healthy RV exhibits robust rhythms in function and molecular gene expression. Cardiovascular disease is the leading cause of mortality in type 1 diabetes (T1D). T1D disrupts circadian rhythms, yet how T1D alters chamber-specific circadian control remains unclear. We investigated RV and LV function and gene expression across the 24-hour light-dark cycle in male streptozotocin-induced T1D and control mice. Echocardiographic assessment of diabetes induced remodeling at ZT0–4 and ZT12–16 (zeitgeber time; ZT) revealed time-dependent functional impairment, including reversal of the normal diurnal heart rate pattern. T1D impaired day-night RV and LV systolic function, with loss of day-night difference in LV ejection fraction and impaired active period RV stroke volume. Cosinor analysis of RV and LV gene expression demonstrated preserved 24-hour rhythmicity of core clock genes Arntl1 and Per2 in both ventricles with T1D, while the clock output genes Nr1d1 and Dbp had dampened amplitude in the RV but amplified expression in the T1D LV. These findings demonstrate that T1D differentially disrupts circadian regulation of the RV and LV, with selective vulnerability of the clock-controlled output genes despite preservation of the core oscillator. Chamber-specific circadian remodeling may contribute to the elevated cardiovascular risk in T1D and has implications for the timing of diagnostic and therapeutic interventions.