MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery

Susannah A A Bloch, Anna V J Donaldson, Amy Lewis, Winston A S Banya, Michael I Polkey, Mark J D Griffiths, Paul R Kemp, Susannah A A Bloch, Anna V J Donaldson, Amy Lewis, Winston A S Banya, Michael I Polkey, Mark J D Griffiths, Paul R Kemp

Abstract

Introduction: Acute muscle wasting in the critically ill is common and associated with significant morbidity and mortality. Although some aetiological factors are recognised and muscle wasting can be detected early with ultrasound, it not possible currently to predict in advance of muscle loss those who will develop muscle wasting. The ability to stratify the risk of muscle wasting associated with critical illness prior to it becoming clinically apparent would provide the opportunity to predict prognosis more accurately and to intervene at an early stage. MicroRNAs are small non-coding RNAs that modulate post-transcriptional regulation of translation, some are tissue specific and can be detected and quantified in plasma. We hypothesised that certain plasma microRNAs could be biomarkers of ICU acquired muscle weakness.

Methods: Plasma levels of selected microRNAs were measured in pre- and post-operative samples from a previously reported prospective observational study of 42 patients undergoing elective high-risk cardiothoracic surgery, 55% of whom developed muscle wasting.

Results: The rise in miR-181a was significantly higher on the second post-operative day in those who developed muscle wasting at 1 week compared to those who did not (p = 0.03). A rise in miR-181a of greater than 1.7 times baseline had 91% specificity and 56% sensitivity for subsequent muscle wasting. Other microRNAs did not show significant differences between the groups.

Conclusion: Plasma miR-181a deserves further investigation as a potential biomarker of muscle wasting. Additionally, since mir-181a is involved in both regulation of inflammation and muscle regeneration and differentiation; our observation therefore also suggests directions for future research.

Figures

Figure 1
Figure 1
Relative plasma microRNA concentration in patients with and without muscle wasting in adult critical care. Relative plasma microRNA concentration in non muscle-wasting (n = 19) and muscle-wasting patients (those with >9.24% muscle loss; n = 23) pre-operatively (PO), on day 1 (D1), day 2 (D2) and on day 7 (D7). Data presented as box and whisker plots with median, interquartile ranges and 5 to 95% percentiles. *P <0.05, **P <0.01, ***P <0.001, repeated measures Freidman’s test with Dunn’s correction for comparison with pre-operative baseline. #P = 0.03 for comparison between groups with the Kolmogorov-Smirnov test.

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