Abstract
BackgroundDespite 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).MethodsOne 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).ResultsMI increased heart/body weight (18%), 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 coli protein and transcription factor jun-D were identified as significantly reduced by Ram treatment.ConclusionsThis 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.
Highlights
Despite major advances in drug development, effective cardiovascular therapies and suitable cardiovascular biomarkers remain limited
Organ weights and infarct size There were no significant increases in heart weight to body weight ratio (HW/BW) amongst the groups, a strong trend toward increased hypertrophy (18%) was observed in myocardial infarction (MI) + vehicle animals compared to sham animals
LV internal diameters in systole (LVIDs) and LVIDd were increased in MI + Veh animals by 107% and 43% respectively; treatment with Ram significantly attenuated the increase in LVIDs and LVIDd by 26% and 17% respectively (Table 2)
Summary
Despite major advances in drug development, effective cardiovascular therapies and suitable cardiovascular biomarkers remain limited. Despite the advancesment in the development of effective therapies for cardiovascular diseases (CVDs), their socioeconomic and human costs continue to escalate throughout the world, with an aging population. The number of effective cardiovascular therapies and viable therapeutic targets remains surprisingly limited. While a powerful tool, often reveals a poor correlation with the quantity of corresponding functional protein. This is probably related to the divergent time course of gene expression in relation to protein expression, regulation and downstream protein production as well as the involvement of other factors. Given the rapid advances in proteomic profiling over the last few years, recent editorials have called for direct and large-scale analysis of proteins within the failing myocardium where significant information may be gained from proteomic approaches [2,3,4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
