| Autor: |
Boteanu RM; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania., Suica VI; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania., Uyy E; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania., Ivan L; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania., Cerveanu-Hogas A; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania., Mares RG; Department of Pathophysiology, University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania., Simionescu M; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania., Schiopu A; Department of Pathophysiology, University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania.; Department of Clinical Sciences Malmö, Lund University, 21428 Malmö, Sweden., Antohe F; Department of Proteomics, Institute of Cellular Biology and Pathology 'N. Simionescu' of the Romanian Academy, 050568 Bucharest, Romania. |
| Abstrakt: |
Prognosis after myocardial infarction (MI) varies greatly depending on the extent of damaged area and the management of biological processes during recovery. Reportedly, the inhibition of the pro-inflammatory S100A9 reduces myocardial damage after MI. We hypothesize that a S100A9 blockade induces changes of major signaling pathways implicated in post-MI healing. Mass spectrometry-based proteomics and gene analyses of infarcted mice left ventricle were performed. The S100A9 blocker (ABR-23890) was given for 3 days after coronary ligation. At 3 and 7 days post-MI, ventricle samples were analyzed versus control and Sham-operated mice. Blockade of S100A9 modulated the expressed proteins involved in five biological processes: leukocyte cell-cell adhesion , regulation of the muscle cell apoptotic process , regulation of the intrinsic apoptotic signaling pathway , sarcomere organization and cardiac muscle hypertrophy . The blocker induced regulation of 36 proteins interacting with or targeted by the cellular tumor antigen p53, prevented myocardial compensatory hypertrophy, and reduced cardiac markers of post-ischemic stress. The blockade effect was prominent at day 7 post-MI when the quantitative features of the ventricle proteome were closer to controls. Blockade of S100A9 restores key biological processes altered post-MI. These processes could be valuable new pharmacological targets for the treatment of ischemic heart. Mass spectrometry data are available via ProteomeXchange with identifier PXD033683. |
