Long Non-Coding RNA HOTTIP is Elevated in Patients with Sepsis and Promotes Cardiac Dysfunction

Immunol Invest. 2022 Oct;51(7):2086-2096. doi: 10.1080/08820139.2022.2107932. Epub 2022 Aug 3.

Abstract

Background: Cardiac dysfunction is the most common clinical complication of sepsis. Herein, the study explored the clinical importance of long non-coding RNA (lncRNA) HOXA terminal transcript antisense RNA (HOTTIP) in the onset of sepsis and the development of cardiac dysfunction.

Methods: 120 patients with sepsis were recruited and divided into cardiac dysfunction group and non-cardiac dysfunction group. Serum HOTTIP levels were measured via RT-qPCR. AC16 cells were treated with lipopolysaccharide (LPS) for cell experiments and detected for cell viability and apoptosis.

Results: High serum HOTTIP levels were tested in sepsis patients, which was associated with procalcitonin (PCT) level. Serum HOTTIP can identify sepsis cases from healthy people with the AUC of 0.927. 72 cases developed into cardiac dysfunction, accompanied by elevated levels of HOTTIP. ROC curve displayed the predictive ability of serum HOTTIP in the development of cardiac dysfunction in patients with sepsis. After adjusting for other clinical parameters, HOTTIP can independently affect the development of cardiac dysfunction. In vitro, HOTTIP knockdown promoted the recovery of cell viability and reversed LPS-induced cell apoptosis and excessive interleukin-6 (IL-6) release.

Conclusion: LncRNA HOTTIP is closely related to the condition of patients with sepsis and the development of cardiac dysfunction, possibly owing to its function in LPS-induced myocardial apoptosis and inflammation.

Keywords: AC16 cell; HOTTIP; cardiac dysfunction; sepsis.

MeSH terms

  • Humans
  • Interleukin-6
  • Lipopolysaccharides
  • MicroRNAs* / genetics
  • Procalcitonin
  • RNA, Antisense
  • RNA, Long Noncoding* / genetics
  • Sepsis* / genetics

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • MicroRNAs
  • Procalcitonin
  • RNA, Antisense
  • RNA, Long Noncoding
  • long noncoding RNA HOTTIP, human