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 R1-antichymotrypsin (R1-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-R-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 R1-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.
Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin alpha1-antichymotrypsin / C. Banfi, A. Parolari, M. Brioschi, S. Barcella, C. Loardi, C. Centenaro, F. Alamanni, L. Mussoni, E. Tremoli. - In: JOURNAL OF PROTEOME RESEARCH. - ISSN 1535-3893. - 9:5(2010), pp. 2347-2357.
|Titolo:||Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin alpha1-antichymotrypsin|
BANFI, CRISTINA (Primo)
PAROLARI, ALESSANDRO (Secondo)
MUSSONI, LUCIANA (Penultimo)
TREMOLI, ELENA (Ultimo)
|Parole Chiave:||Coronary artery bypass grafting; Protease inhibitor; Proteases; Proteomics|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/23 - Chirurgia Cardiaca
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/pr901079v|
|Appare nelle tipologie:||01 - Articolo su periodico|