The intracerebral hemorrhage blood transcriptome in humans differs from the ischemic stroke and vascular risk factor control blood transcriptomes

Abstract

Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH) differs from ischemic stroke (IS) and matched controls (CTRL) will improve understanding of immune and coagulation pathways in both disorders. This study examined RNA from 99 human whole-blood samples using GeneChip® HTA 2.0 arrays to assess differentially expressed transcripts of alternatively spliced genes between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected p(Dx) < 0.2 and p < 0.005 and |FC| > 1.2 for individual comparisons. For time-dependent analyses, subjects were divided into four time-points: 0(CTRL), <24 h, 24-48 h, >48 h; 489 transcripts were differentially expressed between ICH and CTRL, and 63 between IS and CTRL. ICH had differentially expressed T-cell receptor and CD36 genes, and iNOS, TLR, macrophage, and T-helper pathways. IS had more non-coding RNA. ICH and IS both had angiogenesis, CTLA4 in T lymphocytes, CD28 in T helper cells, NFAT regulation of immune response, and glucocorticoid receptor signaling pathways. Self-organizing maps revealed 4357 transcripts changing expression over time in ICH, and 1136 in IS. Understanding ICH and IS transcriptomes will be useful for biomarker development, treatment and prevention strategies, and for evaluating how well animal models recapitulate human ICH and IS.

Prdx1 Reduces Intracerebral Hemorrhage-Induced Brain Injury via Targeting Inflammation- and Apoptosis-Related mRNA Stability

“…RNA-binding protein-mediated posttranscriptional regulation plays an important role in the pathophysiological processes of diseases (Wurth et al, 2016;Bar-Ziv et al, 2019;Baser et al, 2019). Recent studies have shown that posttranscriptional regulation is also associated with ICH (Dykstra-Aiello et al, 2015;Stamova et al, 2019). However, what roles RBPs play in ICH is still largely unknown.…”

“…Accessing posttranscriptional regulation is important to influence the occurrence and development of diseases, such as ICH (Dykstra-Aiello et al, 2015, 2016Stamova et al, 2019). Posttranscriptional regulation includes various processes, such as alternative splicing (AS) (Paschalis et al, 2018), alternative polyadenylation (APA) (Tian and Manley, 2017), gene expression regulation (Roundtree et al, 2017), and RNA methylation (Zhao et al, 2017).…”

“…Moreover, posttranscriptional regulation can be controlled via RBPs (Zhang et al, 2015;Fei et al, 2017). Therefore, targeting posttranscriptional regulation via RBPs may alleviate the brain injury caused by ICH, as the progression of ICH has been shown to be closely regulated by posttranscriptional regulation (Dykstra-Aiello et al, 2015, 2016Stamova et al, 2019).…”

Smoking affects gene expression in blood of patients with ischemic stroke

“…The time of sample collection ranged from 4.4 to 83.2 h after IS. Blood was drawn into PAX gene tubes (Qiagen) and stored frozen at −80°C until processed …”

Biomarkers of Cardiovascular Disease

“…Сравнение транскриптомов крови пациентов с ии и Ги выявило различия в экспрессии ряда факторов. Например, интерлейкины IL-1 и IL-17A, TGFα, HGF и гранулоцитарный колониестимулирующий фактор G-CSF активируются при Ги, но не при ии [115]. Повышенный сывороточный уровень ММР9 может быть точным биомаркером для прогнозирования возникновения церебрального вазоспазма после субарахноидального кровоизлияния [1].…”