Comparative Proteomic Analysis in Left Ventricular Remodeling following Myocardial Infarction in Rats

Objective Left ventricular remodeling （LVR） following myocardial infarction （MI） is a key pathophysiological process in which MI develops into heart failure. The exact mechanism of LVR remains unclear. We performed differential proteomic analysis on the myocardia of rats with LVR after MI, to explore the mechanism of ventricular remodeling after MI. Methods In the LVR group （n=12）, after the anterior descending coronary artery was ligated, the rats were fed for four weeks before the LVR models were established. Rats in the sham-operated group （n=11） underwent thread-drawing without ligation. The hemodynamic parameters, pathological findings, and proteomics were compared between the two groups. Results In the LVR group, the left ventricular end-diastolic pressure increased, the maximal left ventricular pressure increase/decrease ratio decreased significantly, and the left ventricular systolic pressure decreased. H-E staining and Masson staining of cardiac muscle tissues of the LVR group showed myocytolysis, disarray, and collagen proliferation. Twenty-one differentially expressed proteins were detected by proteomic analysis. We validated two proteins using western blot analysis. The differentially expressed proteins could be divided into six categories： energy metabolism-related proteins, cytoskeletal proteins, protein synthesis-related proteins, channel proteins, anti-oxidation- related proteins, and immune-related proteins. Conclusion These differentially expressed proteins might play key roles in LVR following M

Spastin interacts with collapsin response mediator protein 3 to regulate neurite growth and branching

Cytoskeletal microtubule rearrangement and movement are crucial in the repair of spinal cord injury.Spastin plays an important role in the regulation of microtubule severing.Both spastin and collapsin response mediator proteins can regulate neurite growth and branching;however,whether spastin interacts with collapsin response mediator protein 3(CRMP3)during this process remains unclear,as is the mechanism by which CRMP3 participates in the repair of spinal cord injury.In this study,we used a proteomics approach to identify key proteins associated with spinal cord injury repair.We then employed liquid chromatography-mass spectrometry to identify proteins that were able to interact with glutathione S-transferase-spastin.Then,co-immunoprecipitation and staining approaches were used to evaluate potential interactions between spastin and CRMP3.Finally,we co-transfected primary hippocampal neurons with CRMP3 and spastin to evaluate their role in neurite outgrowth.Mass spectrometry identified the role of CRMP3 in the spinal cord injury repair process.Liquid chromatography-mass spectrometry pulldown assays identified three CRMP3 peptides that were able to interact with spastin.CRMP3 and spastin were co-expressed in the spinal cord and were able to interact with one another in vitro and in vivo.Lastly,CRMP3 overexpression was able to enhance the ability of spastin to promote neurite growth and branching.Therefore,our results confirm that spastin and CRMP3 play roles in spinal cord injury repair by regulating neurite growth and branching.These proteins may therefore be novel targets for spinal cord injury repair.The Institutional Animal Care and Use Committee of Jinan University,China approved this study(approval No.IACUS-20181008-03)on October 8,2018.