Elsevier

Progress in Cardiovascular Diseases

Volume 68, September–October 2021, Pages 70-77
Progress in Cardiovascular Diseases

Role of non-coding RNAs as biomarkers of deleterious cardiovascular effects in sepsis

https://doi.org/10.1016/j.pcad.2021.07.005Get rights and content

Abstract

The mechanisms occurring during sepsis that produce an increased risk of cardiovascular (CV) disease (CVD) are poorly understood. Even less information exists regarding CV dysfunction as a complication of sepsis, particularly for sepsis-induced cardiomyopathy. However, recent research has demonstrated that non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, play a crucial role in genetic reprogramming, gene regulation, and inflammation during the development of CVD.

Here we describe experimental findings showing the importance of non-coding RNAs mediating relevant mechanisms underlying CV dysfunction after sepsis, so contributing to sepsis-induced cardiomyopathy. Importantly, non-coding RNAs are critical novel regulators of CVD risk factors. Thus, they are potential candidates to improve diagnostics and prognosis of sepsis-induced cardiomyopathy and other CVD events occurring after sepsis and set the basis to design novel therapeutic strategies.

Section snippets

Background

Sepsis is “a life-threatening condition that arises when the body's response to infection damages its tissues”.1 Despite advances in therapeutic approaches and treatments applied in Intensive Care Units (ICU), sepsis has been estimated to have an incidence of 48 million cases per year worldwide. It continues to be the leading cause of death from infection, counting more than 11 million deaths annually,2 of which nearly 3 million are newborns.3 Moreover, sepsis is the most frequent

Role of MicroRNAs in SIC

miRNAs are conserved, short (17–25 nt) ncRNAs, which regulate gene expression at the posttranscriptional level.26 miRNAs are promising biomarkers in a wide range of diseases due to their ability to control different molecular processes and their stability in various body fluids, like blood, semen, or urine, forming part of exosomes or protein-bound conjugates.27

Interestingly, several studies demonstrated the correlation between the level of circulating miRNAs and the diagnosis and prognosis of

Role of long non-coding RNA in SIC

LncRNAs are a class of regulatory RNA composed of more than 200 nucleotides that are not translated into a protein.43,44 Many studies have revealed the capacity of lncRNAs for remodeling the chromatin and regulating gene expression at transcriptional and post-transcriptional levels in response to various stimuli.45 They can generally be classified as scaffold molecules, guide molecules, decoy molecules, or signaling molecules.45, 46, 47 LncRNAs dysregulation causes an impact on cellular

Role of circular RNA in SIC

circRNA has recently attracted research focused on non-coding RNAs.80 CircRNAs are found free in the cell cytoplasm or stored in exosomes that come from protein-coding or non-coding genes produced by back-splicing process.81 One of the most important characteristics of circRNAs as biomarkers is that circRNAs are present in most mammalian tissues82 but they are highly expressed in specific tissues and development stages.83,84 Moreover, circRNAs usually exhibit higher stability and abundance.85

Conclusions and future perspectives

Recent research in epigenetics, particularly in non-coding RNAs, will contribute to understanding VB injury as a complication of sepsis, especially for SIC and also in CVD after sepsis.

As we described, several non-coding RNAs (lncRNAs, miRNAs, and circRNAs) mediate several mechanisms underlying CV dysfunction in sepsis (Fig. 1), including inflammation, oxidative stress, cardiomyocyte cell death, ischemic cardiomyopathy, myocardial dysfunction, and injury, and activation of vascular endothelial

Funding and acknowledgements and conflict of interest/disclosures

J.B-G. is supported by a Contratos i-PFIS grant (IFI18/00015) and R.O-V. is supported by Contratos PFIS grant (FI20/00202) from AES-ISCIII and co-financed by the European Regional Development Fund (ERDF). E.N-S. is supported by Fundació Mutua Madrileña (AP174352020). F·S-G. is supported by a grant Dr. Juan Peset Aleixandre from the Valencian Medical Institute. J.L.G-G. thanks AES (ISCIII) for grant number PI19/00994, co-financed by ERDF. This research was also supported by Agencia Valenciana de

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