Type 1 Diabetes Differentially Disrupts Right and Left Ventricular Daily Rhythms

Area of Science:

• Cardiovascular Physiology
• Chronobiology
• Metabolic Disease Research

Background:

• Circadian rhythms govern cardiovascular function, with established left ventricle (LV) regulation.
• The right ventricle's (RV) intrinsic circadian rhythmicity and its regulation in disease remain 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 presence of intrinsic circadian rhythms in the healthy RV.
• To determine how T1D alters chamber-specific (RV and LV) circadian control of function and gene expression.
• To explore the implications for T1D-associated cardiovascular risk.

Main Methods:

• Utilized male streptozotocin-induced T1D and control mice.
• Conducted echocardiography across the 24-hour light-dark cycle to assess RV and LV function.
• Performed cosinor analysis on RV and LV gene expression to evaluate circadian rhythmicity of core clock and clock output genes.

Main Results:

• The healthy RV exhibits robust circadian rhythms in function and gene expression.
• T1D induced time-dependent functional impairments in both RV and LV, including reversal of diurnal heart rate patterns.
• T1D selectively disrupted clock output gene rhythmicity (dampened in RV, amplified in LV) despite preserved core clock gene rhythms in both ventricles.

Conclusions:

• T1D differentially disrupts circadian regulation in the RV and LV, with unique vulnerabilities in clock-controlled output genes.
• Chamber-specific circadian remodeling in T1D may contribute to increased cardiovascular risk.
• Findings suggest potential for time-based diagnostic and therapeutic strategies in T1D cardiovascular complications.