Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis

Yue Zheng; Bingcai Qi; Wenqing Gao; Zhenchang Qi; Yanwu Liu; Yuchao Wang; Jianyu Feng; Xian Cheng; Zhiqiang Luo; Tong Li

doi:10.3389/fcvm.2022.890321

Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis

Front Cardiovasc Med. 2022 Jun 30:9:890321. doi: 10.3389/fcvm.2022.890321. eCollection 2022.

Authors

Yue Zheng^{1

2

3

4

5}, Bingcai Qi^{3

4

5

6}, Wenqing Gao^{2

3

4

5

6}, Zhenchang Qi^{3

4

5

6}, Yanwu Liu^{3

4

5

6}, Yuchao Wang^{1

3

4

5

6}, Jianyu Feng^{3

4

5

6}, Xian Cheng^{3

4

5

6}, Zhiqiang Luo^{3

4

5

6}, Tong Li^{1

2

3

4

5

6}

Affiliations

¹ School of Medicine, Nankai University, Tianjin, China.
² Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China.
³ Nankai University Affiliated Third Center Hospital, Tianjin, China.
⁴ The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
⁵ Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.
⁶ Artificial Cell Engineering Technology Research Center, Tianjin, China.

Abstract

Background: The macrophages are involved in all stages of cardiovascular diseases, demonstrating the correlation between inflammation, atherosclerosis, and myocardial infarction (MI). Here, we aim to investigate macrophages-related genes in the deterioration of atherosclerosis.

Methods: GSE41571 was downloaded and the abundance of immune cells was estimated by utilizing the xCell. By utilizing the limma test and correlation analysis, differentially expressed macrophages-related genes (DEMRGs) were documented. The functional pathways and the protein-protein interaction (PPI) network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the expressions of hub DEMRGs were analyzed using the GSE135055 and GSE116250 datasets as well as atherosclerosis and MI mice model.

Results: A total of 509 differentially expressed genes (DEGs) were correlated with the abundance of macrophages and were identified as DEMRGs (Pearson correlation coefficients (PCC) > 0.6), which were mainly enriched in extracellular structure organization, lysosomal membrane, MHC protein complex binding, and so on. After screening out, 28 hub DEMRGs were obtained with degrees ≥20, including GNAI1 (degree = 113), MRPS2 (degree = 56), HCK (degree = 45), SOCS3 (degree = 40), NET1 (degree = 28), and so on. After validating using Gene Expression Omnibus (GEO) datasets and the atherosclerosis and MI mice model, eight proteins were validated using ApoE-/- and C57 mice. The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.

Conclusion: The screened hub DEMRGs, SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, EIF4EBP1, and PPP4C, may be therapeutic targets for treatment and prediction in the patients with plaque progression and MI recurrent events. The kit of the eight hub DEMRGs may test plaque progression and MI recurrent events and help in the diagnosis and treatment of MI-induced heart failure (HF), thus decreasing mortality and morbidity.

Keywords: GO/KEGG pathways analysis; GSEA; PPI; atherosclerosis; differentially expressed genes; immune infiltration; macrophages; progression.