# Integrated analysis reveals the dysfunction of intercellular communication and metabolic signals in dilated cardiomyopathy

## TL;DR

This study identifies disrupted cell communication and metabolic pathways in dilated cardiomyopathy, offering new insights into disease mechanisms and potential treatment targets.

## Contribution

The study integrates single-nucleus and bulk RNA sequencing data to reveal cell-type-specific disruptions in intercellular communication and metabolism in dilated cardiomyopathy.

## Key findings

- Cell-cell communication is abnormal in dilated cardiomyopathy, with distinct alterations in different cell types.
- Metabolic pathways for glucose, lipid, and amino acid are impaired in a cell-specific manner in dilated cardiomyopathy.
- Dysfunctional BMP, NOTCH, and arginine metabolism gene expression is validated in dilated cardiomyopathy.

## Abstract

Dilated cardiomyopathy refers to a heart muscle condition characterized by structural and functional irregularities in the myocardium that are not related to ischemia. Due to diverse etiologies such as genetic mutations, infections, and exposure to toxins, dilated cardiomyopathy can lead to substantial morbidity and mortality despite advances in the management of heart failure in dilated cardiomyopathy patients. We sought to analyze the characteristics of cell-cell communication and the metabolic signaling pathways in dilated cardiomyopathy.

The single-nucleus sequencing data of left ventricle samples were acquired from two donor datasets and two dilated cardiomyopathy datasets. Three dilated cardiomyopathy bulk-sequencing datasets were included to determine the shared dilated cardiomyopathy-specific alterations in differentially expressed genes and signaling pathways. Using “CellChat,” we analyzed intercellular communication to grasp how cell clusters interact and to map out the impaired signaling pathways in both donor and dilated cardiomyopathy conditions. Gene set enrichment analysis was applied to compare the metabolic signaling before and after dilated cardiomyopathy. We showcased how cell clusters exhibited abnormal cell-to-cell signaling transduction and how each cell type displayed dysfunctional metabolic signaling pathways through the integration of various datasets. The crucial ligand-receptor signaling contributing to outgoing or incoming signaling of dilated cardiomyopathy was identified in a cell-type dependent way, and the cell-specific metabolic alterations in glucose, lipid and amino acid were determined. The expression of gene pairs in BMP and NOTCH signal, as well as the gene expression in the arginine metabolism was validated.

We reveal the key signals and metabolic pathways for dilated cardiomyopathy adaptation and maintenance, providing potential targets for dilated cardiomyopathy interference.

A summary figure for DCM pathology. Toxins, viruses, and genetic mutations play pivotal roles in instigating abnormalities within the heart, leading to disruptions in vital processes such as cell-to-cell communication, signal transduction, and metabolism. These disturbances ultimately culminate in the onset of DCM.Image 1

•In DCM, the communication between cells is abnormal.•Various cell types exhibit distinct alterations in their cell-cell signaling transduction pathways in DCM.•Dysfunctional metabolic changes occur in DCM.•Glucose, lipid, and amino acid pathways are impaired in a cell specific manner in DCM.

In DCM, the communication between cells is abnormal.

Various cell types exhibit distinct alterations in their cell-cell signaling transduction pathways in DCM.

Dysfunctional metabolic changes occur in DCM.

Glucose, lipid, and amino acid pathways are impaired in a cell specific manner in DCM.