Skeletal Muscle Microvascular Dysfunction Manifests Early in Diabetic Cardiomyopathy.

Area of Science:

• Cardiovascular Research
• Metabolic Diseases
• Animal Models

Background:

• Type II diabetes is linked to cardiac dysfunction and exercise intolerance.
• The precise timing and interplay of microvascular dysfunction, cardiac changes, and exercise capacity in diabetes remain unclear.

Purpose of the Study:

• To investigate the temporal sequence of microvascular dysfunction, cardiac dysfunction, and exercise intolerance in a rat model of type II diabetes.
• To gain insights into the early pathogenesis of diabetic cardiomyopathy.

Main Methods:

• A non-obese, diet-induced, low-dose streptozotocin model was used in male rats over 10 months.
• Deep cardiac phenotyping included echocardiography, treadmill exercise tests, photoacoustic imaging, flow-mediated dilation, blood analysis, and histology.
• Skeletal muscle and myocardial perfusion were assessed.

Main Results:

• Early skeletal muscle microvascular dysfunction and reduced exercise tolerance were observed (4 months).
• Diabetic rats showed early diastolic and mild systolic cardiac dysfunction, with preserved ejection fraction, resembling heart failure with preserved ejection fraction (HFpEF).
• Myocardial perfusion remained normal, and key HFpEF markers (fibrosis, hypertrophy, rarefaction) were absent in the heart and skeletal muscle.

Conclusions:

• Skeletal muscle microvascular dysfunction is an early event in type II diabetes, preceding hypertension and contributing to exercise intolerance and cardiac dysfunction.
• The observed cardiac dysfunction in diabetic rats aligns with HFpEF, despite the absence of typical associated pathologies.
• This study highlights the critical role of peripheral microvascular changes in the development of diabetic heart disease.