Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users

Jie Jia; Ji-Qun Yang; Ying-Rong Du; Yu Xu; Deshenyue Kong; Xiu-Ling Zhang; Jun-Hong Mao; Gui-Fang Hu; Kun-Hua Wang; Yi-Qun Kuang

doi:10.2147/JIR.S361634

Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users

J Inflamm Res. 2022 Jun 9:15:3409-3420. doi: 10.2147/JIR.S361634. eCollection 2022.

Authors

Jie Jia^{1

2}, Ji-Qun Yang³, Ying-Rong Du³, Yu Xu², Deshenyue Kong^{1

2}, Xiu-Ling Zhang³, Jun-Hong Mao^{1

2}, Gui-Fang Hu³, Kun-Hua Wang^{1

2

4}, Yi-Qun Kuang^{1

2}

Affiliations

¹ NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People's Republic of China.
² Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People's Republic of China.
³ Third People's Hospital of Kunming City/Drug Rehabilitation Hospital of Kunming City, Kunming, 650041, People's Republic of China.
⁴ School of Medicine, Yunnan University, Kunming, 650500, People's Republic of China.

Abstract

Background: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown.

Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS).

Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log₂(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8⁺ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR.

Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.

Keywords: drug use; hypertension; immunoregulation; transcriptome; treatment-resistant.

Grants and funding

This work was partly supported by the National Natural Science Foundation of China (81660094), the Fund for Yunling Scholar (YLXL20170002), the General Joint Project of the Department of Science and Technology of Yunnan Province and Kunming Medical University (2017FE467(-038), 2017FE467(-130)), the Project for Innovation Team of Department of Science and Technology of Yunnan Province, China (2018HC005), the Fund of Department of Education of Yunnan Province (2019Y0352), the Fund of Health Commission of Yunnan Province (2018NS0085), the Fund of Yunnan Provincial Clinical Research Center for General Surgical Diseases (zx2019-03-03) and Yunnan Provincial Clinical Research Center for Skin Immune Diseases (2019ZF012) from Science and Technology Department of Yunnan Province, Yunnan Fundamental Research Projects (2202201AT070292 and 202201AU070202) and the Doctoral Research Fund of First Affiliated Hospital of Kunming Medical University (2020BS003).