Type 1 Diabetes Differentially Disrupts Right and Left Ventricular Daily Rhythms

Area of Science:

• Cardiovascular physiology
• Chronobiology
• Metabolic disease research

Background:

• Circadian rhythms regulate cardiovascular function, particularly the left ventricle (LV).
• The right ventricle's (RV) intrinsic circadian rhythmicity and its regulation in disease remain largely unknown.
• Cardiovascular disease is a major complication of type 1 diabetes (T1D), which is known to disrupt circadian rhythms.

Purpose of the Study:

• To investigate the intrinsic circadian rhythmicity of the healthy RV.
• To determine how T1D alters chamber-specific (RV and LV) circadian regulation of function and gene expression.
• To explore the implications for cardiovascular risk in T1D.

Main Methods:

• Investigated RV and LV function and gene expression over a 24-hour light-dark cycle in male streptozotocin-induced T1D and control mice.
• Utilized echocardiography to assess cardiac function and remodeling.
• Performed cosinor analysis on gene expression data for core clock and clock output genes.

Main Results:

• The healthy RV exhibits robust circadian rhythms in function and gene expression.
• T1D impaired diurnal RV and LV systolic function, altering heart rate patterns and reducing LV ejection fraction and RV stroke volume.
• While core clock genes (Arntl1, Per2) maintained rhythmicity, T1D differentially affected clock output genes (Nr1d1, Dbp) in the RV and LV.

Conclusions:

• T1D differentially disrupts circadian regulation in the RV and LV, with selective vulnerability in clock-controlled output genes.
• Preserved core clock oscillator function contrasts with altered clock output gene expression.
• Chamber-specific circadian remodeling in T1D may contribute to elevated cardiovascular risk and suggests timing-dependent diagnostic and therapeutic strategies.