Mapping the cellular and molecular landscape of cardiac non-myocytes in murine diabetic cardiomyopathy

Diabetes is associated with a significantly elevated risk of heart failure. However, despite extensive efforts to characterize the phenotype of the diabetic heart, the molecular and cellular protagonists that underpin cardiac pathological remodeling in diabetes remain unclear, with a notable paucity of data regarding the impact of diabetes on non-myocytes within the heart. Here we aimed to define key differences in cardiac non-myocytes between spontaneously type-2 diabetic (db/db) and healthy control (db/h) mouse hearts. Single-cell transcriptomic analysis revealed a concerted diabetes-induced cellular response contributing to cardiac remodeling. These included cell-specific activation of gene programs relating to fibroblast hyperplasia and cell migration, and dysregulation of pathways involving vascular homeostasis and protein folding. This work offers a new perspective for understanding the cellular mediators of diabetes-induced cardiac pathology, and pathways that may be targeted to address the cardiac complications associated with diabetes.

Automated summary

Diabetes is associated with an increased risk of heart failure, but the impact of diabetes on non-myocytes in the heart is still unclear. This study found that diabetes-induced cardiac remodeling involves a cellular response, including activation of fibroblast hyperplasia, cell migration, and dysregulation of pathways related to vascular homeostasis and protein folding.