Investigation of Metabolism in Hypertrophic Cardiomyopathy
Abstract
In the Discovery Award Application, titled 'Investigation of metabolism in hypertrophic cardiomyopathy' (CDMRP Discovery Award, Log Number:PR171587), we proposed compilation of metabolite profiles (non-targeted metabolomics) from heart tissue and targeted quantitation of candidate plasma metabolite biomarkers at early stage of disease (5 weeks of age) in 2 mouse models of hypertrophic cardiomyopathy (R403Q-MyHC, R92W-TnT) and littermate control mice. Metabolomics was proposed 1) at rest and during dobutamine-stress (inotrope stimulation) at 5 weeks of age, and 2) following 6weeks of 120 min/day of swim exercise (starting at 5 weeks of age) in the swim and age-matched non-swim group. we hypothesized 1) presence of differences in cardiac metabolism in early disease stage between mutants and age-matched controls, and that 2) acute increase in cardiac work (induced by dobutamine) or chronic increase in cardiac work (resulting from intense daily swimming) would result in mutation-specific changes in cardiac metabolic remodeling and plasma metabolite levels. Using non-targeted metabolomics that yielded >1000 annotated metabolites across 3 platforms (GC-TOF, HILIC-Triple TOF MS, CSH-QTOF MS/MS)we discovered allele-specific, marked differences in cardiac metabolism at baseline, and differences in the cardiac metabolic response to dobutamine in the mouse models at 5 weeks of age. Furthermore, the 2 mouse models also exhibited differences in cardiac metabolic remodeling following exercise training.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1110776
Entities
People
- Maria Roselle Abraham
Organizations
- University of California Regents