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.
Highlights
Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection [1, 2]
Sepsis-induced cardiac dysfunction is challenged by a lack of uniformity in its definition of incidence, prognosis, and clinical importance
Two other core problems are whether cardiac dysfunction definitely contributes to poor outcome or prognosis, or is a reflection of organ failure in general, and the degree to which sepsis-induced cardiac dysfunction is adaptive or pathological [4]
Summary
Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection [1, 2]. Epidemiological studies showed that ∼28.3 to 41% of all hospitalized sepsis patients died due to multiple organ failure [5], and sepsis-induced cardiac dysfunction (SICD) was identified as being closely associated with higher mortality rates [6, 7]. Long non-coding RNA (lncRNA) is a type of ncRNA that is composed of more than 200 nucleotides and contributes to transcriptional and post-transcriptional regulation of RNA. Activation of inflammatory pathways mediated by Toll-like receptor (TLR) signaling in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) is an important mechanism of cardiomyocyte injuries caused by sepsis. The lncRNAs involved in both sepsis and cardiovascular diseases (CVD) among individual studies are described and their potential associations in SICD are analyzed; these studies were treated as indirect evidence for the role of lncRNAs in SICD
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