INTRODUCTION. Body mass index (BMI) is used to determine body fat based on height and weight. Obesity, classified as BMI>30.0, is a known risk factor for cardiovascular disease, notably acute cerebrovascular disease. It is thought that obesity promotes a chronic state of inflammation due to increased adiposity. It is unclear whether this chronic state of inflammation is protective in the event of cerebrovascular diseases such as ischemic and hemorrhagic stroke. MicroRNA (miRNA) are key regulators of post-translational gene expression. In this study, we examine circulating miRNA profile and inflammatory biomarkers that may complement and provide more objective diagnostic criteria for the paradoxical association between BMI and intracerebral hemorrhage (ICH).
METHODS. After informed consent, patients with acute spontaneous ICH (n=16) were consented and blood samples collected within 48 hrs of admission. Samples were grouped according to BMI-Low (<30) v BMI-High (>30). Total RNA containing small RNA were isolated from Paxgene Blood RNA samples and used to profile 2,515 known miRNA using uParaflo Microfluidic Biochip. Gene expression was carried out using RNAseq and EgdeR (v3.12.1). Gene set enrichment analysis (GSEA) for KEGG pathways and Gene Ontology (GO) were done using GAGE (v2.20.1) and miRWalk 2.0.
RESULTS. In plasma, we found 23 highly expressed miRNA, 11 of which were downregulated in BMI-H (Table 1; Figure 1). GSEA for KEGG pathways and GO showed enrichment for protein translation and ribosome biogenesis for upregulated genes in BMI-H. Conversely, GSEA of downregulated genes in BMI-H favored inflammation and recruitment of cytokines and signaling. Importantly, KEGG pathway analysis identified pathways significantly enriched involving TNF signaling and cytokine-cytokine receptor interaction. However, pro-inflammatory cytokines were found to be upregulated in BMI-H vs BMI-L, notably DPPIV, MMP-9, ENA-78, IL-17A (Figure 3). 
CONCLUSION. In our study, there was paradoxical lower expression of pro-inflammatory genes in BMI-H compared to BMI-L. However, proteins level were higher in BMI-H suggesting a possible epigenetic effect such as from miRNA expression.

BMI-INTRACEREBRAL HEMORRHAGE PARADOX: THE ROLE OF INFLAMMATORY CYTOKINES AND MICRORNA PROFILE