Metabolic Adjustments by LncRNAs in Peripheral Neutrophils Partly Account for the Complete Compensation of Asymptomatic MMD Patients

Abstract

Background: Due to the recent development of non-invasive examinations, more asymptomatic patients with Moyamoya Disease (MMD) have been diagnosed than ever. However, its underlying molecular mechanisms and clinical intervention guidelines are all still obscure.

Methods: Microarray was used to explore those differentially expressed mRNAs and lncRNAs in peripheral neutrophils of asymptomatic MMD patients. Then enrichment analyses based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for those differentially expressed mRNAs and lncRNA associated mRNAs were performed for underlying molecular mechanisms.

Results: Here, we identified a total of 2824 differentially expressed lncRNAs and 522 differentially expressed mRNAs (fold change > 2 and P<0.05) in peripheral neutrophils of asymptomatic MMD patients, compared with healthy controls. Then enrichment analyses based on GO and KEGG showed that the neighboring protein-coding mRNAs of those up-regulated and down-regulated lncRNAs were mainly involved in distinct metabolic processes respectively, which may act as a complementary response to insufficient blood supplies in MMD. Further enrichment analyses of those differentially expressed mRNAs preferentially listed essential physiological processes such as peptide cross-linking, chromatin assembly among others. Moreover, altered mRNAs also revealed to be enriched in renin secretion, platelet activation, inflammation and others.

Conclusion: We demonstrated for the first time that metabolic adjustments by dysregulated lncRNAs in peripheral neutrophils might partially account for the complete compensation of asymptomatic MMD patients. In addition, more attention should be paid on renin secretion and platelet activation in order to better understand the pathogenesis and guide clinical intervention for asymptomatic MMDs.

Keywords: LncRNAs; asymptomatic; bioinformatics; microarray; moyamoya disease; neutrophils.