Integrative Omics Analysis Identifies Biomarkers of Septic Cardiomyopathy
Kexin Cai, Yuqing Luo, Hongyin Chen, Yanfang Dong, Yunyun Su, Chen Lin, Chuanqi Cai, Yikbin Shi, Siming Lin, Guili Lian, Zhihong Lin, Shaodan Feng.
Abstract
Septic Cardiomyopathy (SCM) is a syndrome of acute cardiac dysfunction in septic patients, unrelated to cardiac ischemia. Multiomics studies including transcriptomics and proteomics have provided new insights into the mechanisms of SCM. In here, a rat model of SCM was established by intraperitoneal injection of lipopolysaccharide (LPS). Biomarkers of SCM were characterized via a multi-omics analysis. The differentially expressed (DE) mRNAs predominantly appeared in pathways linked to the immune response, inflammatory response, and the complement and coagulation cascades, while DE proteins were mainly enriched in pathways associated with the complement and coagulation cascades.
Introduction
Sepsis is characterized as a critical organ malfunction resulting from an uncontrolled host reaction to infection. Epidemiological studies reported that between 28.3% and 41% of patients with sepsis die of multiple organ failure after hospital admission. Due to its high morbidity and mortality rates, sepsis is considered among the top ten leading causes of death worldwide, especially lethal among critically ill patients, with 50 million cases and 11 million deaths per year.
Materials and Methods:
Myocardial tissue from each rat was separately fixed in 4% paraformaldehyde, followed by gradual dehydration in an ethanol solution, paraffin embedding, 4-μm sections preparation, hematoxylin-eosin (HE) staining, and photography under a light microscope (Nikon, Japan). A portion of the remaining myocardial tissue was preserved on TRIzol reagent (Invitrogen, China) for RNA extraction, the rest was immediately snap-frozen and stored at -80°C for subsequent protein extraction.
Discussion
SCM is considered a common but extremely serious complication of sepsis. While the dysregulation of the host’s immune response is linked to the impairment of organ function, the pathophysiological mechanisms underlying sepsis-induced cardiac alterations are intricate and influenced by various factors, the pathogenesis of which remains unclear. This study aimed to systematically investigate the molecular mechanism underlying SCM in rats by analyzing the transcriptomic and proteomic profiles of heart tissue. We characterized the changes and related biological pathways of various genes and proteins in the rat heart.
Acknowledgments
We want to thank the participants and the participating physicians at the First Affiliated Hospital of Fujian Medical University.
Citation: Cai K, Luo Y, Chen H, Dong Y, Su Y, Lin C, et al. (2024) Integrative omics analysis identifies biomarkers of septic cardiomyopathy. PLoS ONE 19(11): e0310412. https://doi.org/10.1371/journal.pone.0310412
Editor: Jon M. Jacobs, Pacific Northwest National Laboratory, UNITED STATES OF AMERICA
Received: April 4, 2024; Accepted: August 30, 2024; Published: November 15, 2024.
Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting information files.
Funding: This work is supported by the Fujian Provincial Financial Health and Health Provincial Special Subsidy Funds (grant number: BPB-2022 FSD and BPB-FSD2021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
