Proteomic Analysis of Plasma from Patients Undergoing Coronary Artery Bypass Grafting Reveals a Protease/Antiprotease Imbalance in Favor of the Serpin α1-Antichymotrypsin

Abstract

We used proteomics to identify systematic changes in the plasma proteins of patients undergoing coronary artery bypass grafting (CABG) by means of cardiopulmonary bypass surgery. It is known that, after CABG, a complex systemic inflammatory responses ensues that favors the occurrence of adverse postoperative complications frequently recognizing inflammation itself and/or thrombosis as the underlying mechanism. We found a marked and persistent postoperative increase in the levels of the serpin-protease inhibitor alpha(1)-antichymotrypsin (alpha(1)-ACT) that fully maintains the inhibitory activity blunting its protease substrate cathepsin G. An intraoperative increase followed by a rapid decline in proteases activation was documented, accompanied by a substantial induction of leucine-rich-alpha-2-glycoprotein, a protein involved in neutrophilic granulocyte differentiation. Finally, a time-dependent alteration in the expression of haptoglobin, transthyretin, clusterin, and apoE was observed. In conclusion, we showed that after CABG, a protease/antiprotease imbalance occurs with early cathepsin G activation and a more delayed increase in alpha(1)-ACT. As cathepsin G is a serpin involved both in inflammation and coagulation activation, this confirms and expands the concept of a marked dysregulation of both inflammatory and hemostatic balances occurring after CABG. The pharmacologic modulation of this imbalance may be a new therapeutic target to reduce postoperative complications.

Post-transcriptional Regulation of α-1-Antichymotrypsin by MicroRNA-137 in Chronic Heart Failure and Mechanical Support

“…Downloaded from http://ahajournals.org by on April 27, 2019 Likewise, ACT was elevated during the first days after an acute coronary syndrome, 32,33 and a persistent postoperative increase was noticed after coronary artery bypass grafting. 34 Apart from this important role of ACT as a modulator between inflammation and progression of HF by extracellular mechanisms, it may also have important intracellular effects. ACT has the unique ability among serpins to bind to DNA, a property that is independent of its serine protease inhibitory activity.…”

Normal human mitral valve proteome: A preliminary investigation by gel‐based and gel‐free proteomic approaches

“…Equal amounts of proteins from mitral valve tissue from five subjects dissolved in urea buffer containing bromophenol blue were pooled together and 0.8% ampholytes pH 3–10 were added. 2‐DE was carried out on Protean IEF cell (Bio‐Rad, Milan, Italy) according to the manufacturer's protocol as previously described . For further details, please see Supporting Information.…”

Proteomic analysis in cardiovascular research

“…The proteomic approach has been receiving much attention in this clinical area. Proteomic analyses of plasma taken from patients undergoing coronary artery bypass grafting with CPB revealed that a protease/antiprotease imbalance develops after surgery, with early activation of cathepsin G (a serpin involved both in inflammation and coagulation activation), and then a delayed increase in alpha 1-antichymotrypsin (an inhibitor of neutrophil cathepsin G) [ 55 ] (Table 3 ). This imbalance is consistent with the postoperative systemic inflammatory response and dysregulation of hemostatic balance.…”