Right ventricular dysfunction in preclinical models of type I and type II diabetes

Area of Science:

• Cardiology
• Metabolic Diseases
• Molecular Biology

Background:

• Diabetic cardiomyopathy (DCM) is linked to diabetes mellitus and heart failure, primarily studied in the left ventricle (LV).
• Right ventricular (RV) dysfunction significantly impacts mortality but remains understudied in diabetic contexts.
• Distinct RV physiology necessitates investigation into diabetes-specific RV pathophysiology.

Purpose of the Study:

• To investigate RV-specific pathophysiology in mouse and pig models of diabetes.
• To identify unique metabolic and functional changes in the RV due to diabetes.
• To determine if RV changes in DCM differ from those in the LV.

Main Methods:

• Utilized a type 2 diabetes mellitus (T2DM) mouse model (high-fat diet, streptozotocin) and a type I diabetes pig model (streptozotocin).
• Assessed RV global and systolic function, hypertrophic and fibrotic remodeling.
• Analyzed RV insulin sensitivity, metabolic gene expression, mitochondrial dynamics, antioxidant gene expression, and fatty acid uptake regulators.

Main Results:

• Diabetes induced RV dysfunction, hypertrophy, and fibrosis in both models.
• Impaired RV insulin sensitivity, dysregulated metabolic gene expression, and altered mitochondrial dynamics were observed.
• Unlike the LV, the RV showed unchanged antioxidant gene expression and fatty acid uptake regulators in T2DM mice.

Conclusions:

• Diabetes significantly impacts RV function and structure, independent of LV changes.
• RV-specific pathophysiology in DCM warrants further investigation.
• The findings support the development of novel, RV-targeted therapeutic strategies for diabetic heart conditions.