Proteomic Analysis of Plasma from Patients Undergoing Coronary Artery Bypass Grafting Reveals a Protease/Antiprotease Imbalance in Favor of the Serpin α1-Antichymotrypsin
| Autor: | Maura Brioschi, Francesco Alamanni, Luciana Mussoni, Chiara Centenaro, Alessandro Parolari, Simona Barcella, Cristina Banfi, Elena Tremoli, Claudia Loardi |
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| Přispěvatelé: | Banfi, C, Parolari, A, Brioschi, M, Barcella, S, Loardi, C, Centenaro, C, Alamanni, F, Mussoni, L, Tremoli, E |
| Rok vydání: | 2010 |
| Předmět: |
Male
Proteomics Proteases Cathepsin G Bypass grafting alpha 1-Antichymotrypsin medicine.medical_treatment Molecular Sequence Data Coronary artery bypass grafting Pharmacology Serpin Biochemistry Apolipoproteins E Humans Prealbumin Medicine Amino Acid Sequence Coronary Artery Bypass Immunoelectrophoresis Glycoproteins Analysis of Variance Protease Haptoglobins business.industry Proteomic Reproducibility of Results General Chemistry Middle Aged Blood proteins Protease inhibitor (biology) Clusterin surgical procedures operative medicine.anatomical_structure Protease inhibitor sense organs business Peptide Hydrolases Artery medicine.drug |
| Zdroj: | Journal of Proteome Research. 9:2347-2357 |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/pr901079v |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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