Application of Animal Models in Diabetic Cardiomyopathy

Abstract

Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

Keywords: Cardiomyopathies; Diabetes mellitus; Disease models, animal; Heart failure.

Fig. 1.

Pathological and functional changes of diabetic cardiomyopathy. The pathologies of the diabetic hearts show that the increases in reactive oxygen species generation, apoptosis, cardiac hypertrophy, mitochondrial dysfunction, and myocardial fibrosis than non-diabetic heart. Diabetes mellitus (vs. no diabetes mellitus) is also associated with heart failure with preserved ejection fraction characterized by reduced compliance (reduced mitral E/A ratio) and diastolic dysfunction. ROS, reactive oxygen species; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; RV, right ventricle; LV, left ventricle.