» Articles » PMID: 37736052

Mapping the Cellular and Molecular Landscape of Cardiac Non-myocytes in Murine Diabetic Cardiomyopathy

Abstract

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 () and healthy control 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.

Citing Articles

Integrative Single-Cell Analysis of Cardiomyopathy Identifies Differences in Cell Stemness and Transcriptional Regulatory Networks among Fibroblast Subpopulations.

Nie W, Zhao Z, Liu Y, Wang Y, Zhang J, Hu Y Cardiol Res Pract. 2024; 2024:3131633.

PMID: 38799173 PMC: 11127766. DOI: 10.1155/2024/3131633.

References
1.
Miranda-Silva D, Wust R, Conceicao G, Goncalves-Rodrigues P, Goncalves N, Goncalves A . Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction. Acta Physiol (Oxf). 2019; 228(3):e13378. PMC: 7064935. DOI: 10.1111/apha.13378. View

2.
Kusters D, Chatrou M, Willems B, De Saint-Hubert M, Bauwens M, van der Vorst E . Pharmacological Treatment with Annexin A1 Reduces Atherosclerotic Plaque Burden in LDLR-/- Mice on Western Type Diet. PLoS One. 2015; 10(6):e0130484. PMC: 4475013. DOI: 10.1371/journal.pone.0130484. View

3.
Huang A, Yang Y, Yan C, Kaley G, Hintze T, Sun D . Altered MAPK signaling in progressive deterioration of endothelial function in diabetic mice. Diabetes. 2012; 61(12):3181-8. PMC: 3501862. DOI: 10.2337/db12-0559. View

4.
Krstevski C, Cohen C, Dona M, Pinto A . New perspectives of the cardiac cellular landscape: mapping cellular mediators of cardiac fibrosis using single-cell transcriptomics. Biochem Soc Trans. 2020; 48(6):2483-2493. DOI: 10.1042/BST20191255. View

5.
Gusarova V, ODushlaine C, Teslovich T, Benotti P, Mirshahi T, Gottesman O . Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes. Nat Commun. 2018; 9(1):2252. PMC: 5997992. DOI: 10.1038/s41467-018-04611-z. View