In a murine model, diabetes induced by streptozotocin and a high-fat diet resulted in diastolic dysfunction and a significant 2.36-fold increase in cardiac fibroblasts compared to non-diabetic controls.
In a murine model, diabetes-induced diastolic dysfunction is associated with significant increases in cardiac fibroblasts and systemic monocytosis, highlighting potential cellular targets for diabetic cardiomyopathy.
Effect estimate: 2.36-fold increase
p-value: p=<0.0001
Abstract Background Diabetes is associated with a significantly elevated risk of cardiovascular disease and its specific pathophysiology remains unclear. Recent studies have changed our understanding of cardiac cellularity, with cellular changes accompanying diabetes yet to be examined in detail. This study aims to characterise the changes in the cardiac cellular landscape in murine diabetes to identify potential cellular protagonists in the diabetic heart. Methods Diabetes was induced in male FVB/N mice by low-dose streptozotocin and a high-fat diet for 26-weeks. Cardiac function was measured by echocardiography at endpoint. Flow cytometry was performed on cardiac ventricles as well as blood, spleen, and bone-marrow at endpoint from non-diabetic and diabetic mice. To validate flow cytometry results, immunofluorescence staining was conducted on left-ventricles of age-matched mice. Results Mice with diabetes exhibited hyperglycaemia and impaired glucose tolerance at endpoint. Echocardiography revealed reduced E:A and e’:a’ ratios in diabetic mice indicating diastolic dysfunction. Systolic function was not different between the experimental groups. Detailed examination of cardiac cellularity found resident mesenchymal cells (RMCs) were elevated as a result of diabetes, due to a marked increase in cardiac fibroblasts, while smooth muscle cells were reduced in proportion. Moreover, we found increased levels of Ly6C hi monocytes in both the heart and in the blood. Consistent with this, the proportion of bone-marrow haematopoietic stem cells were increased in diabetic mice. Conclusions Murine diabetes results in distinct changes in cardiac cellularity. These changes—in particular increased levels of fibroblasts—offer a framework for understanding how cardiac cellularity changes in diabetes. The results also point to new cellular mechanisms in this context, which may further aid in development of pharmacotherapies to allay the progression of cardiomyopathy associated with diabetes.
Cohen et al. (Tue,) conducted a other in Diabetes-induced cardiomyopathy (n=26). Streptozotocin and high-fat diet vs. Citrate vehicle control and standard chow diet was evaluated on Proportion of cardiac fibroblasts (2.36-fold increase, p=<0.0001). In a murine model, diabetes induced by streptozotocin and a high-fat diet resulted in diastolic dysfunction and a significant 2.36-fold increase in cardiac fibroblasts compared to non-diabetic controls.
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