A metabolomic and proteomic investigation of the pathology underlying the induction and reversal of heart failure

UoM administered thesis: Phd

  • Authors:
  • Amy Watkins

Abstract

Heart failure (HF) affects 1-2% of the population in developed countries; however, the underlying metabolic processes are still not completely understood. This study used an ovine tachypacing model of HF to investigate this important gap in knowledge. This model recovers upon the cessation of pacing therefore allowing us to examine not only the induction but also the reversal of HF. This approach could identify novel pathways which could be targeted to improve cardiac function. HF was induced in female Welsh sheep by transvenous right ventricular tachy-pacing at 210 bpm until symptomatic HF was established. Another cohort of animals was allowed to recover for five weeks at the point of HF. Metabolites were then extracted from LV tissue samples, using a MeOH:CHCl3 ‘Folch style’ method, with polar extracts taken from the MeOH phase to be analysed by GC-MS, and non-polar extracts from the CHCl3 phase to be measured by LC-MS. Protein was also extracted from cardiac LV samples, and digested, iTRAQ-labelled and analysed by a LC-MS/MS-based methodology. Data were analysed using ProteinPilot with a UniProt database, and protein expression changes were analysed using Ingenuity Pathway Analysis (IPA). Relative levels of the glycolytic intermediates glucose and glucose-6-phosphate were significantly increased and decreased respectively (both q

Details

Original languageEnglish
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Award date1 Aug 2018