Plasma Proteomic Profiling Of Cardiac Operation- Related Muscle Loss

Abstract

Cardiac aortic operation can cause significant muscle loss in some patients, which can then lead to a longer recovery period, frailty in the long-term and eventually, to mortality. Although the loss caused by the disturb of the normal balance between degradation/synthesis signalling pathway, the dynamics response of proteins following the cardiac-operation to promote muscle loss have yet to be investigated. Our study used co- expression and differential network analysis to compare the plasma proteome expression of 30 male patients (median= 70 years, and interquartile range (IQR) = 60-74.75). Muscle mass and strengths loss were measured pre-operation, and post-operation at the 7th day using physical performance and ultrasound. Blood sample collection was also taken pre- operation, and post-operation at day one to correlate with skeletal muscle parameter. The clinical outcome showed variability ranging from no muscle mass loss to significant loss (median was 8.65% (IQR= 1.94%,13.19%)), leg strength at 9.31% (IQR= -0.64%,13.27%) and hand strength at 15.74% (IQR= -0.63%, 34.46%). The correlation analysis of the plasma protein (n=1299) with muscle loss showed large numbers of promising significant proteins, of which three were associated with mass and strength loss; Granulocyte-macrophage colony-stimulating factor (GM-CSF), Macrophage-capping protein (CAPG), and NudC domain-containing protein 3 (NUDC3). In addition, strength loss association strongly with Fibroblast growth factor 23 (FGF23) (R-value= 0.71, P-value= 1.3E-05), as well as Growth differentiation factor 15 (GDF15/MIC-1) (R-value=0.65, P-value= 1.08E-04). Our findings suggest potential pharmacological intervention including targeting GM-CSF and CAPG, in- vivo experiment to discover novel pathway by NUDC3, FGF23 and MIC-1 in muscle wasting where other group of proteins might involve in promoting muscle loss.