Peptidomic profiles of post myocardial infarction rats affinity depleted plasma using matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) mass spectrometry

Background: Despite major advances in drug development, effective cardiovascular therapies and suitable cardiovascular biomarkers remain limited. The aim of this study was to leverage mass spectrometry (MS) based peptide profiling strategies to identify changes that occur in peptidomic profiles of rat plasma following coronary artery ligation generated myocardial infarction (MI). Methods: One week after MI, rats were randomized to receive either an ACE inhibitor (ramipril, Ram-1 mg/kg/day), or vehicle (Veh) for 12 weeks. Echocardiography and hemodynamic measurements were made before sacrifice and plasma collection. High abundance proteins were depleted with affinity capture before MS profiling. Differentially expressed peptide ions were identified using proprietary software (ClinProtTools). Results: MI increased heart/body weight (180), lung/body weight (56%), and left ventricular (LV) end diastolic pressure (LVEDP, 247%); and significantly reduced percentage fractional shortening (FS, 75%) and rate of pressure rise in the LV (dP/dtmax, 20%). Ram treatment significantly attenuated the changes in LVEDP (61%) and FS (27%). Analysis of MALDI-ToF generated mass spectra demonstrated that peptide ions 1271, 1878, 1955, 2041 and 2254 m/z were consistently decreased by Ram treatment (p < 0.001) and thus may be associated with the agent's therapeutic effects. Among peptides that were significantly changed, synapsin-2, adenomatous polyposis coil protein and transcription factor jun-D were identified as significantly reduced by Ram treatment. Conclusions: This approach allows us to screen for potential biomarkers in a window of the blood proteome that previously has been difficult to access. The data obtained from such an approach may potentially useful in prognosis, diagnosis, and monitoring of treatment response.