Proteomics Study Of Early Ventricular Remodeling After Acute Myocardial Infarction

[Aims] Myocardial infarction (MI) is the main etiology of chronic heart failure. Post-infarct remodelling contributes mostly to the development of post-infarct heart failure. In this study, we are intended to utilize comparative proteomics to analysis myocardial tissue of border zone during early stage of post-infarct remodelling on acute myocardial infarction (AMI) rat model, so as to explore the potential molecular mechanism of post-infarct remodelling.[Methods and results] Firstly, AMI model was produced successfully in rat using mechanical ventilation and in situ suturing. Secondly, dynamic observation was done on morphological and histological alterations in heart after AMI and active histological change was found in border zone with obvious time-course:infiltration of acute inflammation cells, mainly neutrophils and apoptosis of myocardial cells began from one day post-infarction. On day4, chronic inflammation cells and formation of de novo granulation tissue was observed with neovascularization and proliferation of fibroblasts. Evident fibrosis showed in border zone on day10. Accordingly, we divided early stage of post-infarct remodeling into three phases:inflammation phase, proliferation phase and maturation phase, and day1,4and10post-infarction was selected to present the three phases. Based on these, comparative proteomics platform of two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF) were used to identify the differential protein profiles expressed in the border zone at specific time points (days0,1,4, and10post-infarction) in a permanent rat MI model. We identified96differential protein spots, corresponding to69proteins. Cluster analysis exhibited mainly three temporal expression patterns corresponding to the three phases of early stage post-infarct remodelling. Bioinformatics analysis showed that these differential proteins be functionally associated with a variety of biological events, such as ischemia injury, oxidative stress, inflammation response and proliferation, et al. Finally, three differential proteins, including cofilin-1, SNAP-29and prohibitin, were selected to be analyzed with reverse transcription PCR (RT-PCR), western blotting and immunohistochemistry. Proteomics results were validated and preliminary quantitative and localization information were obtained of the three proteins functionally associated with early post-infarct remodelling.[Conclusions] To produce AMI model in rat, utilizing mechanical ventilation and in-situ suturing made a stable and successful result, which is easy to handle and suitable to spread. Active histological change was found in border zone with obvious time course, and day1,4and10post-infarction could present three phases of early post-infarct remodeling (inflammation, proliferation and maturation phases), which is in accordance with early literatures. A differential myocardial proteome profile was identified in the border zone during early stage post-infarct remodelling. Bioinformatics analysis indicated possible roles of these proteins in remodelling. Proteomics results provided potential molecular mechanism of early post-infarct remodelling and the basis for further functional study of these proteins and for identifying potential molecular targets with therapeutic anti-remodelling effects.