TY - JOUR
T1 - Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin α1-antichymotrypsin
AU - Banfi, Cristina
AU - Parolari, Alessandro
AU - Brioschi, Maura
AU - Barcella, Simona
AU - Loardi, Claudia
AU - Centenaro, Chiara
AU - Alamanni, Francesco
AU - Mussoni, Luciana
AU - Tremoli, Elena
PY - 2010/5/7
Y1 - 2010/5/7
N2 - 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 serin-protease inhibitor α1-antichymotrypsin (α1-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-α- 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 α1-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.
AB - 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 serin-protease inhibitor α1-antichymotrypsin (α1-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-α- 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 α1-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.
KW - Coronary artery bypass grafting
KW - Protease inhibitor
KW - Proteases
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=77952085953&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952085953&partnerID=8YFLogxK
U2 - 10.1021/pr901079v
DO - 10.1021/pr901079v
M3 - Article
C2 - 20302328
AN - SCOPUS:77952085953
VL - 9
SP - 2347
EP - 2357
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 5
ER -