AUTHOR=Laudanski Krzysztof , Liu Da , Gullipalli Damodar , Song Wen-Chao , Okeke Tony , Szeto Wilson Y. 

TITLE=A decline of protective apolipoprotein J and complement factor H concomitant with increase in C5a 3 months after cardiac surgery—Evidence of long-term complement perturbations

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.983617

DOI=10.3389/fcvm.2022.983617

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Heart surgery results in complement activation with the potential for collateral end-organ damage, especially if the protective elements (complement factor H, Apolipoprotein J) are inadequate. Here, we have investigated if peri-operative stress results in an imbalance between complement activation and its protective mechanisms up to 3 months after heart surgery.</p></sec><sec><title>Methods</title><p>101 patients scheduled for non-emergent cardiac surgery donated blood before the procedure (t<sub>baseline</sub>), and 24 h (t<sub>24<italic>h</italic></sub>), 7 days (t<sub>7<italic>d</italic></sub>) and 3 months (t<sub>3<italic>m</italic></sub>) after. Complement activation was measured as a serum level of soluble activated component 5 (sC5a) and soluble terminal complement complex (sTCC). Simultaneously, protective complement factor H (CfH), and apolipoprotein J (ApoJ) were measured. Inflammatory responses were quantified using C-reactive protein (CRP) and interleukin-6 (IL-6). Details regarding anesthesia, intensive care unit (ICU) stay, pre-existing conditions, the incidence of postoperative complications, and mortality were collected from medical records.</p></sec><sec><title>Results</title><p>C5a declined at t<sub>24<italic>h</italic></sub> to rebound at t<sub>7<italic>d</italic></sub> and t<sub>3<italic>m</italic></sub>. sTCC was significantly depressed at t<sub>24<italic>h</italic></sub> and returned to baseline at later time points. In contrast, CfH and ApoJ were depressed at t<sub>3<italic>m</italic></sub>. Milieu of complement factors aligned along two longitudinal patterns:cluster#1 (C5a/sTTC continuously increasing and CfH/ApoJ preserved at t<sub>baseline</sub>) and cluster#2 (transient sC5a/sTTC increase and progressive decline of CfH). Most patients belonged to cluster #1 at t<sub>24<italic>h</italic></sub> (68%), t<sub>7d</sub> (74%) and t<sub>3m</sub> (72%). sTCC correlated with APACHE<sub>1<italic>h</italic></sub> (<italic>r</italic><sup>2</sup> =−0.25; <italic>p</italic> &lt; 0.031) and APACHE<sub>24<italic>h</italic></sub> (<italic>r</italic><sup>2</sup> = 0.27; <italic>p</italic> &lt; 0.049). IL-6 correlated with C5a (<italic>r</italic><sup>2</sup> =−0.28; <italic>p</italic> &lt; 0.042) and sTTC (<italic>r</italic><sup>2</sup> =−0.28; <italic>p</italic> &lt; 0.015). Peri-operative administration of acetaminophen and aspirin altered the complement elements. Prolonged hospital stay correlated with elevated C5a [<italic>t</italic> (78) = 2.03; <italic>p</italic> = 0.048] and sTTC serum levels [<italic>U</italic> (73) = 2.07; <italic>p</italic> = 0.037]. Patients with stroke had a decreased serum level of C5a at t<sub>7d</sub> and t<sub>3m</sub>.</p></sec><sec><title>Conclusion</title><p>There is a significant decrease in complement protective factors 3 months after cardiac surgery, while C5a seems to be slightly elevated, suggesting that cardiac surgery affects complement milieu long into recovery.</p></sec>