The heterocellular heart: identities, interactions, and implications for cardiology

Abstract

The heterocellular nature of the heart has been receiving increasing attention in recent years. In addition to cardiomyocytes as the prototypical cell type of the heart, non-myocytes such as endothelial cells, fibroblasts, or immune cells are coming more into focus. The rise of single-cell sequencing technologies enables identification of ever more subtle differences and has reignited the question of what defines a cell’s identity. Here we provide an overview of the major cardiac cell types, describe their roles in homeostasis, and outline recent findings on non-canonical functions that may be of relevance for cardiology. We highlight modes of biochemical and biophysical interactions between different cardiac cell types and discuss the potential implications of the heterocellular nature of the heart for basic research and therapeutic interventions.

Nonpreferential but Detrimental Accumulation of Macrophages With Clonal Hematopoiesis-Driver Mutations in Cardiovascular Tissues—Brief Report

“…The formation of carotid artery plaques involves excessive lipid deposition, endothelial damage, and inflammatory immunocyte infiltration at the lesions, [32][33][34] while heart diseases encompass malfunctioning cardiomyocytes, fibroblasts, and imbalanced immune activities in response to intrinsic or extrinsic (eg, ischemia, valvular defects) triggers. [35][36][37] Overall, our data manifest that the DNMT3A and TET2 mutations associate with inflammatory macrophages in both cardiovascular tissues.…”

Mineralocorticoid receptor promotes cardiac macrophage inflammaging

“…The heart contains heterogeneous subsets of resident macrophages [ 6 , 16 , 17 , 42 ]. Having discovered that MR deletion prevents macrophage polarization toward a pro-inflammatory phenotype in the aging heart, we next determined whether there were associated changes in the number and proportion of macrophage subsets.…”

“…Resident macrophages are gatekeepers of tissue homeostasis and integrity and prime cells involved in initiation and regulation of inflammatory responses [ 5 , 61 ]. Heterogeneous populations of macrophages deriving from embryonic progenitors as well as bone marrow precursor cells co-exist in the heart [ 6 , 42 ]. Age-dependent alterations in the cardiac microenvironment and intrinsic dysregulations can lead to phenotypic and functional changes in resident macrophages that could have profound effects on cardiac aging [ 32 , 34 , 58 , 59 ].…”

Catecholamine treatment induces reversible heart injury and cardiomyocyte gene expression

“…The heart is composed of numerous cell types that show distinct gene expression profiles [ 30 ]. To assess the impact of catecholamine treatment on cardiomyocyte gene expression, mRNA expression in isolated cardiomyocyte nuclei was determined by RNA-seq (Fig.…”

“…To elucidate the underlying molecular mechanisms involved in that process, we studied the transcriptional response to IsoPE in cardiomyocytes. This approach allowed us to decipher the regulation of signaling pathways within a given cell type in a less biased manner compared to the analysis of cardiac tissue [ 27 , 30 , 38 ]. Studies comparing the effects of combined IsoPE treatment to isoprenaline alone indicated that concurrent activation of α-adrenergic receptors enhances the effect of isoprenaline on cardiac remodeling and gene expression [ 15 , 35 ].…”