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other·cardiology, endocrinology, preclinical research, biomedical research·PMC10509303

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

iScience · 15 authors, 8 centres

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TL;DR

This preclinical study used single-cell transcriptomics to profile cardiac non-myocytes in a mouse model of type-2 diabetes (db/db) versus non-diabetic controls. The central result was that type-2 diabetes alters the abundance and gene expression of virtually all cardiac non-myocyte cell populations, with key changes preceding and potentially driving cardiac remodeling.

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This preclinical study used single-cell RNA sequencing to map cardiac non-myocyte populations in 17-week-old db/db leptin-receptor mutant mice (a model of type-2 diabetes) and age-matched heterozygous non-diabetic littermate controls. These changes occurred alongside early signs of diastolic dysfunction but before significant fibrosis.

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other

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cardiology

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ORIGINAL PAPER

PMC10509303

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

iScience

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ABSTRACT

Summary 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. Subject areas: Molecular biology, Cell biology, Omics, Transcriptomics

CITATION EXPORT

Charles D Cohen, Miles J De Blasio, Gabriella E Farrugia et al.. Mapping the cellular and molecular landscape of cardiac non-myocytes in murine diabetic cardiomyopathy. iScience. (2023). https://doi.org/10.1016/j.isci.2023.107759

AUTHORS

15 · 8 CENTRES

Charles D Cohen, Miles J De Blasio, Gabriella E Farrugia, Malathi SI Dona, Ian Hsu, Darnel Prakoso, Helen Kiriazis, Crisdion Krstevski, David M Nash, Mandy Li, Taylah L Gaynor, Minh Deo, Grant R Drummond, Rebecca H Ritchie, Alexander R Pinto

1Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
2Preclinical Cardiology, Microsurgery and Imaging Platform, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
3Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
4Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, Australia
5Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
6Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC, Australia
7Baker Department of Cardiovascular Research and Implementation, La Trobe University, Melbourne, VIC, Australia
8Department of Pharmacology, Monash University, Clayton, VIC, Australia