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Comprehensive Transcriptome and Metabolome Profiling Reveals Key Regulating Signaling and Metabolic Pathways of Resistant Hypertension in Drug Users

SSRN Electronic Journal
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  • Usage
    236
    • Abstract Views
      204
    • Downloads
      32

Article Description

Background: Hypertension is a common complication in drug user, and hypertension patients with drug use have a low susceptibility to hypotensor. The pathogenesis and metabolic characteristics of hypertension in drug user remain unknown. Methods: We performed high-throughput sequencing for transcriptome and metabonomic of peripheral blood from 30 hypertension patients with drug use ( HBP-DU ) and 30 hypertension patients without drug use (HBP) to investigate the key signaling moieties and metabolites in hypertension induced by drug use. Findings: The results showed that 17 upregulated, 2 downregulated genes and 19 upregulated, 8 downregulated metabolites in HBP-DU group compared with HBP group. Differentially expressed genes (DEGs) were mainly involved in the immune process, including toll-like receptor (TLR) cascades, FCERI signaling and interleukin signaling. Differentiallymetabolites (DMs) were significantly enriched in the pathways of alanine and histidine metabolism. Further, we identified a gene cluster (turquoise module, MEturquoise ) correlated with HBP-DU by weighted gene co-expression network analysis (WGCNA). Functional analysis shows a similar function of MEturquoise to DEGs. Correlation analysis demonstrated that hippurate was positively associated with most DEGs in HBP rather than in HBP-DU group. Further, immune cell infiltration analysis demonstrated that the abundance of CD4+ T cells and CD8+ T cells was significantly decreased in HBP-DU group. Interpretation: These results indicated a potential function of histidine, immune cells and the pathway of toll-like receptor cascades in hypertension induced by drug use. Funding: This work was partly supported by Yunnan Fundamental Research Projects (2202201AT070292 and 202201AU070202), the Doctoral Research Fund of First Affiliated Hospital of Kunming Medical University (2020BS003), the Scientific Research Fund of the Education Department of the Yunnan Province(2022J0224). Declaration of Interest: None to declare. Ethical Approval: This study was approved by the review board of Third People’s Hospital of Kunming City, and the experimental protocols were approved by the institutional review board of the institutions (No. 2018-L-42). All subjects provided their written informed consent for inclusion before they participated in this study.

Bibliographic Details

Ji-Qun Yang; Jie Jia; Yu Zhao; Wei-Jie Wang; Tong Chen; Ying-Rong Du; Gui-Fang Hu; Jun Li; Ming-Chun Wang; Yi-Qun Kuang

Elsevier BV

drug use; hypertension; metabolite; transcriptome; immunoregulation

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