Proteomic analysis of plasma from patients undergoing coronary artery bypass grafting reveals a protease/antiprotease imbalance in favor of the serpin alpha1-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.

• Authors: Cristina Banfi, Alessandro Parolari, Maura Brioschi, Simona Barcella, Claudia Loardi, Chiara Centenaro, Francesco Alamanni, Luciana Mussoni, Elena Tremoli
• Journal: Journal of proteome research (J Proteome Res) Vol. 9 Issue 5 Pg. 2347-57 (May 07 2010) ISSN: 1535-3907 [Electronic] United States
• PMID: 20302328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Clusterin
• Glycoproteins
• Haptoglobins
• LRG1 protein, human
• Prealbumin
• alpha 1-Antichymotrypsin
• Peptide Hydrolases
• Cathepsin G

Topics

• Amino Acid Sequence
• Analysis of Variance
• Apolipoproteins E (blood)
• Cathepsin G (blood)
• Clusterin (blood)
• Coronary Artery Bypass
• Glycoproteins (blood)
• Haptoglobins (metabolism)
• Humans
• Immunoelectrophoresis
• Male
• Middle Aged
• Molecular Sequence Data
• Peptide Hydrolases (blood)
• Prealbumin (metabolism)
• Proteomics (methods)
• Reproducibility of Results
• alpha 1-Antichymotrypsin (blood, metabolism)