Integrated application of transcriptome and metabolomics reveals potential therapeutic targets for the polarization of atherosclerotic macrophages

Lin Shen; Han Li; Weiqian Chen; Yanping Su; Junchao Yu; Minjiang Chen; Gaofeng Shu; Enqi Qiao; Xiaoju Guo; Min Xu; Shuiwei Xia; Zhongwei Zhao; Chenying Lu; Jiansong Ji

doi:10.1016/j.bbadis.2022.166550

Integrated application of transcriptome and metabolomics reveals potential therapeutic targets for the polarization of atherosclerotic macrophages

Biochim Biophys Acta Mol Basis Dis. 2022 Dec 1;1868(12):166550. doi: 10.1016/j.bbadis.2022.166550. Epub 2022 Sep 20.

Authors

Lin Shen¹, Han Li², Weiqian Chen¹, Yanping Su¹, Junchao Yu¹, Minjiang Chen¹, Gaofeng Shu¹, Enqi Qiao¹, Xiaoju Guo¹, Min Xu¹, Shuiwei Xia¹, Zhongwei Zhao³, Chenying Lu⁴, Jiansong Ji⁵

Affiliations

¹ Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of Interventional Radiology, Clinical College of The Affiliated Central Hospital of Lishui University, Lishui 323000, China.
² Department of Endocrinology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
³ Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of Interventional Radiology, Clinical College of The Affiliated Central Hospital of Lishui University, Lishui 323000, China. Electronic address: zhaozw79@163.com.
⁴ Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of Interventional Radiology, Clinical College of The Affiliated Central Hospital of Lishui University, Lishui 323000, China. Electronic address: luchenying@zju.edu.cn.
⁵ Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Department of Interventional Radiology, Clinical College of The Affiliated Central Hospital of Lishui University, Lishui 323000, China. Electronic address: jijiansong@zju.edu.cn.

PMID: 36150660
DOI: 10.1016/j.bbadis.2022.166550

Abstract

The polarization of macrophages often leads to severe calcification and necrosis in aged atherosclerotic plaques, which eventually leads to poor prognosis of ischaemic cardiovascular and cerebrovascular diseases. More reliable diagnostic methods are urgently needed to discover therapeutic targets of macrophage polarization in aged atherosclerotic plaques. Metabolomics of aged plaques (n = 20) and macrophage polarization transcriptomes (n = 30) were integrated to identify metabolic therapeutic targets of macrophage polarization associated with aged plaque. Finally, metabolic inhibitors were used to verify the reliability of the target genes. Integrated multiomics analysis revealed that 6 metabolic pathways (including 21 genes) regulate macrophage polarization in aged atherosclerosis. Targeted treatment of macrophage polarization with metabolic inhibitors can effectively reduce the adverse risk of aged atherosclerosis. The combination of transcriptomics and metabolomics approaches can identify effective therapeutic targets for macrophage polarization in arteriosclerosis.

Keywords: Atherosclerotic plaque; Macrophage polarization; Metabonomics; Multimomics analysis; Transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atherosclerosis* / drug therapy
Atherosclerosis* / genetics
Atherosclerosis* / metabolism
Humans
Macrophages / metabolism
Metabolomics
Plaque, Atherosclerotic* / drug therapy
Plaque, Atherosclerotic* / genetics
Plaque, Atherosclerotic* / metabolism
Reproducibility of Results
Transcriptome