Characterising an Alternative Murine Model of Diabetic Cardiomyopathy

Abstract

The increasing burden of heart failure globally can be partly attributed to the increased prevalence of diabetes, and the subsequent development of a distinct form of heart failure known as diabetic cardiomyopathy. Despite this, effective treatment options have remained elusive, due partly to the lack of an experimental model that adequately mimics human disease. In the current study, we combined three consecutive daily injections of low-dose streptozotocin with high-fat diet, in order to recapitulate the long-term complications of diabetes, with a specific focus on the diabetic heart. At 26 weeks of diabetes, several metabolic changes were observed including elevated blood glucose, glycated haemoglobin, plasma insulin and plasma C-peptide. Further analysis of organs commonly affected by diabetes revealed diabetic nephropathy, underlined by renal functional and structural abnormalities, as well as progressive liver damage. In addition, this protocol led to robust left ventricular diastolic dysfunction at 26 weeks with preserved systolic function, a key characteristic of patients with type 2 diabetes-induced cardiomyopathy. These observations corresponded with cardiac structural changes, namely an increase in myocardial fibrosis, as well as activation of several cardiac signalling pathways previously implicated in disease progression. It is hoped that development of an appropriate model will help to understand some the pathophysiological mechanisms underlying the accelerated progression of diabetic complications, leading ultimately to more efficacious treatment options.

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

“…The mechanism underlying this process are multifactorial and poorly understood. As a result, no treatment is available to prevent or reverse this pathological change (Kawamura et al, 2017;Lorenzo-Almorós et al, 2017;Tate et al, 2019).…”

Diastolic Dysfunction in a Pre-clinical Model of Diabetes Is Associated With Changes in the Cardiac Non-myocyte Cellular Composition

“…Second, we only examined male mice in our study. Given that cardiac pathology is sex-speci c in mice [11,12] and in humans [16,45], cardiac cellular composition and gene expression are sexually-dimorphic [46]. Future work should examine the impact of biological sex in the development of diabetic cardiomyopathy.…”

Application of Animal Models in Diabetic Cardiomyopathy

“…The prevalence of diabetes mellitus (DM) is increasing at a critical rate; recent assumptions predict that 642 million adults worldwide will be affected by DM by 2040 [ 1 , 2 ]. Importantly, diabetic patients have an increased risk of chronic complications, including retinopathy, neuropathy, nephropathy, and cardiovascular disease [ 1 , 3 , 4 ].…”

“…DM elicits changes in several cell types in the heart, including cardiac fibroblasts, endothelial cells, cardiomyocytes, and inflammatory cells. These changes promote detrimental cardiac remodeling, including cardiac fibrosis, cardiomyocyte apoptosis, and myocardial hypertrophy [ 1 , 9 , 10 ].…”