MicroRNA (miRNA): A New Dimension in the Pathogenesis of Antiphospholipid Syndrome (APS)

Abstract

MicroRNAs (miRNAs) are single-stranded, endogenous RNA molecules that play a significant role in the regulation of gene expression as well as cell development, differentiation, and function. Recent data suggest that these small molecules are responsible for the regulation of immune responses. Therefore, they may act as potent modulators of the immune system and play an important role in the development of several autoimmune diseases. Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by venous and/or arterial thromboses and/or recurrent fetal losses in the presence of antiphospholipid antibodies (aPLs). Several lines of evidence suggest that like other autoimmune disorders, miRNAs are deeply involved in the pathogenesis of APS, interacting with the function of innate and adaptive immune responses. In this review, we characterize miRNAs in the light of having a functional role in the immune system and autoimmune responses focusing on APS. In addition, we also discuss miRNAs as potential biomarkers and target molecules in treating APS.

Keywords: APS; MicroRNA; antiphospholipid syndrome; autoimmunity; miRNA.

Figure 1

A. A partially unknown stimulus referred to as a first hit (i.e., DAMPs, PAMPs, and aPLs) stimulates TLRs, which in turn activate signal pathways resulting in activation of proinflammatory cytokine genes. B. As the result of inflammatory gene activation, synthesis of inflammatory cytokines and expression of adhesion molecules (i.e., ICAM-1 and VCAM-1) on the endothelium surface occurs. C. Permissive background creates procoagulatory milieu to perpetuate a shift towards coagulation and endothelial damage. D. As the result of suppression of regulatory miRNA (marked in red), the immune system is shifted towards active proinflammatory response with Th polarization toward Th1 and Th17 responses, subsequent activation of B-cells, and autoantibody secretion (including aPLs) causing inflammatory storm (activation of endothelium and clothing factors). All the crucial steps are precisely regulated at the level of miRNAs, which mainly suppress (red text) but also (to a lesser degree) activate (green text) procoagulation. Abbreviations: miRNAs = microRNAs, APS = antiphospholipid syndrome, PAMPs = pathogen-associated molecular patterns, DAMPs = danger-associated molecular patterns, TLRs = toll-like receptors, TRAF6 = tumor necrosis factor receptor-associated factor 6, JAK/STAT = janus kinases/signal transducer and activator of transcription, NF-κB = nuclear factor kappa-B, MAPK = mitogen-activated protein kinase, mTOR = mechanistic target of rapamycin, aPLs = antiphospholipid antibodies.