The Diabetic Cardiac Fibroblast: Mechanisms Underlying Phenotype and Function

Diabetic cardiomyopathy involves remodeling of the heart in response to diabetes that includes microvascular damage, cardiomyocyte hypertrophy, and cardiac fibrosis. Cardiac fibrosis is a major contributor to diastolic dysfunction that can ultimately result in heart failure with preserved ejection fraction. Cardiac fibroblasts are the final effector cell in the process of cardiac fibrosis. This review article aims to describe the cardiac fibroblast phenotype in response to high-glucose conditions that mimic the diabetic state, as well as to explain the pathways underlying this phenotype. As such, this review focuses on studies conducted on isolated cardiac fibroblasts. We also describe molecules that appear to oppose the pro-fibrotic actions of high glucose on cardiac fibroblasts. This represents a major gap in knowledge in the field that needs to be addressed.