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

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 |log 2 (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.

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

“…DNA library was constructed according to the work ow as described previously [3]. Total RNA was isolated from peripheral blood using TRIzol reagent (Invitrogen, Carlsbad, CA, USA) following the procedure.…”

“…Drug use, one of the major public health issues in the world nowadays, is a serious threat to healthy individuals. Drug use not only imposes a severe dysregulation of the peripheral immune response but also contributes to the development of hypertension [2], which is characterized by a high proportion of drug-resistant [3]. However, the relationship between drug use and hypertension remains unknown.…”