The role of microRNAs in muscle wasting and recovery during critical illness: a systematic review

Abstract

IntroductionCritical illness associated with intensive care unit (ICU) admission often results in persistent skeletal muscle wasting and may lead to frailty in older and patients with multi‐morbidity. Early recognition of patients at high‐risk of long‐term complications could provide opportunities to minimize the impact of critical illness and improve health and quality of life. MicroRNAs (miRs) are short, non‐coding RNAs that regulate approximately two‐thirds of the human genome and are involved in most biological processes. Multiple studies have demonstrated their role in muscle development and disease and their potential as biomarkers of muscle wasting.Aim and methodsThis systematic review examined the potential of miRs as biomarkers and therapeutics for muscle wasting during and following critical illness. PubMed and Scopus databases were searched for terms associated with critical illness, ICU, muscle wasting, frailty and microRNAs from inception to June 2022 (PROSPERO number CRD42022339531).ResultsOut of 537 articles, seven studies met the inclusion criteria and examined skeletal muscle and circulating miRs in the context of muscle wasting and/or frailty related to critical illness. Across the seven studies, 27 different miRs were identified that were reported to be dysregulated in the muscle and four in the blood, plasma or serum of critically ill patients. Four miRs were reported to be altered in both muscle and blood during critical illness and their levels moderately correlated with parameters of muscle function. These included canonical muscle‐enriched miRs (myomiRs), such as miR‐133, miR‐1 and miR‐181, which correlated with muscle strength in critically ill patients. However, most of the miRs reported to be dysregulated in the muscle following critical illness were examined in one article only.ConclusionsThis systematic review highlights the potential of miRs as biomarkers of skeletal muscle wasting and ICU‐associated weakness following critical illness, suggesting the need for larger validation studies using unbiased techniques. We have described circulating and muscle microRNAs, which correlated with muscle parameters during critical illness. However, the limited number of studies in this area highlights the requirement for further studies before these could be considered in clinical practice.

The role of microRNAs in critical illness—do miRs truly ‘miRror’ muscle wasting?

“…A systematic review by Borja-Gonzalez et al focused on these characteristics of miRs and approached the role of miRs in muscle wasting and recovery during critical illness. 15 They examined the expression levels of miRs in muscle and circulation in the context of muscle weakness and/or frailty related to critical illness and revealed that 27 different miRs were dysregulated in muscle and 4 in blood from seven studies that met their inclusion criteria. In patients with ICU-AW, miR-424-5p and miR-542-3p/miR-542-5p levels in muscle correlated with muscle mass and strength, increased during ICU stay, and decreased 7 days after ICU discharge.…”