3 research outputs found
ShortâTerm Blockade of ProâInflammatory Alarmin S100A9 Favorably Modulates Left Ventricle Proteome and Related Signaling Pathways Involved in PostâMyocardial Infarction Recovery
Prognosis after myocardial infarction (MI) varies greatly depending on the extent of dam-aged area and the management of biological processes during recovery. Reportedly, the inhibition of the proâinflammatory S100A9 reduces myocardial damage after MI. We hypothesize that a S100A9 blockade induces changes of major signaling pathways implicated in postâMI healing. Mass spectrometryâbased proteomics and gene analyses of infarcted mice left ventricle were performed. The S100A9 blocker (ABRâ23890) was given for 3 days after coronary ligation. At 3 and 7 days postâ MI, ventricle samples were analyzed versus control and Shamâoperated mice. Blockade of S100A9 modulated the expressed proteins involved in five biological processes: leukocyte cellâcell adhesion, regulation of the muscle cell apoptotic process, regulation of the intrinsic apoptotic signaling pathway, sarco-mere organization and cardiac muscle hypertrophy. The blocker induced regulation of 36 proteins inter-acting with or targeted by the cellular tumor antigen p53, prevented myocardial compensatory hy-pertrophy, and reduced cardiac markers of postâischemic stress. The blockade effect was prominent at day 7 postâMI when the quantitative features of the ventricle proteome were closer to controls. Blockade of S100A9 restores key biological processes altered postâMI. These processes could be val-uable new pharmacological targets for the treatment of ischemic heart. Mass spectrometry data are available via ProteomeXchange with identifier PXD033683