The Role of Long Non-coding RNAs in Sepsis-Induced Cardiac Dysfunction

Abstract

Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. The heart is one of the most commonly involved organs during sepsis, and cardiac dysfunction, which is usually indicative of an extremely poor clinical outcome, is a leading cause of death in septic cases. Despite substantial improvements in the understanding of the mechanisms that contribute to the origin and responses to sepsis, the prognosis of sepsis-induced cardiac dysfunction (SICD) remains poor and its molecular pathophysiological changes are not well-characterized. The recently discovered group of mediators known as long non-coding RNAs (lncRNAs) have presented novel insights and opportunities to explore the mechanisms and development of SICD and may provide new targets for diagnosis and therapeutic strategies. LncRNAs are RNA transcripts of more than 200 nucleotides with limited or no protein-coding potential. Evidence has rapidly accumulated from numerous studies on how lncRNAs function in associated regulatory circuits during SICD. This review outlines the direct evidence of the effect of lncRNAs on SICD based on clinical trials and animal studies. Furthermore, potential functional lncRNAs in SICD that have been identified in sepsis studies are summarized with a proven biological function in research on other cardiovascular diseases.

Keywords: biomarker; cardiac dysfunction; gene therapy; long non-coding RNA; sepsis.

Figure 1

The schematic diagram describes classification of lncRNA functions. (A) LncRNAs guide ribonucleoprotein complexes to specific location of chromatin. (B) LncRNAs support assembly of protein complex. (C) lncRNAs serve as molecular signals for tissue and temporary specific activation of transcription. (D) LncRNAs can alter splicing patterns of mRNA and suppress transcription by sequestering transcription factors. (E) LncRNAs can bind to and take away protein factors, such as transcription factors and chromatin modifiers, to influence transcriptome. (F) LncRNA can “sponge” miRNA by base pairing with their complementary base sequence and reduce their effects (G) lncRNAs may interact with a variety of RNA binding proteins (RBPs), leading to alternations of mRNA stability, splicing, protein stability and subcellular localization.

Figure 2

The schematic diagram describes the involved lncRNAs in sepsis induced cardiac dysfunction (SICD). Generally, current evidences demonstrated some lncRNAs served as biomarkers for SCID. Then, monocytes, macrophage, and mast cells would be activated with kinds of cytokines secretion. After that, immune responses of cardiomyocytes would lead to mitochondrial dysfunction, apoptosis and autophagy under the regulation of specific lncRNAs. Besides, lncRNAs also participates in the regulation of endothelial cells and smooth muscle cells during SICD.