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Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts
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Title: | Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts |
Authors: | Gowda, Siddabasave Gowda B. Browse this author →KAKEN DB | Gowda, Divyavani Browse this author | Hou, Fengjue Browse this author | Chiba, Hitoshi Browse this author →KAKEN DB | Parcha, Vibhu Browse this author | Arora, Pankaj Browse this author | Halade, Ganesh V. Browse this author | Hui, Shu-Ping Browse this author →KAKEN DB |
Keywords: | Heart failure | Inflammation biomarker | Multivariate analysis | Echocardiography | Histology | Lipidomics | Liquid chromatography/Mass spectrometry |
Issue Date: | Dec-2022 |
Publisher: | Elsevier |
Journal Title: | Atherosclerosis |
Volume: | 363 |
Start Page: | 30 |
End Page: | 41 |
Publisher DOI: | 10.1016/j.atherosclerosis.2022.11.005 |
PMID: | 36455306 |
Abstract: | Background and aims: Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF. Methods: Here, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echo-cardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naive controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed. Results: In humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/ 16:0)) was observed in mouse tissues and plasma in chronic HF. Conclusions: Overall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF. |
Rights: | © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/90789 |
Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 惠 淑萍
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