Abstract
Clinical variation in patient responses to myocardial infarction (MI) has been difficult to model in laboratory animals. To assess the genetic basis of variation in outcomes after heart attack, we characterized responses to acute MI in the Collaborative Cross (CC), a multi-parental panel of genetically diverse mouse strains. Striking differences in post-MI functional, morphological, and myocardial scar features were detected across 32 CC founder and recombinant inbred strains. Transcriptomic analyses revealed a plausible link between increased intrinsic cardiac oxidative phosphorylation levels and MI-induced heart failure. The emergence of significant quantitative trait loci for several post-MI traits indicates that utilizing CC strains is a valid approach for gene network discovery in cardiovascular disease, enabling more accurate clinical risk assessment and prediction.
Document Type
Journal Article
Funding Information
...This work was supported by National Health and Medical Research Council (NHMRC) Australia Fellowship (546133, N.A.R.), Australian Research Council (ARC) Stem Cells Australia (SR1100102, N.A.R.), NHMRC/Heart Foundation Career Development Fellowship (1049980, M.R.), a trampoline grant from the Association Française contre les Myopathies (17822, K.J.N.), an Australian Research Council Future Fellowship (FT100100734, K.J.N.), an NHMRC Program Grant (1037321, G.M.), an NHMRC Project Grant (1069173, G.M.), and the Diabetes Research Foundation of WA (G.M.), a United States National Institutes of Health Research Grant (R01HL116449, J.W.H.).
School
School of Medical and Health Sciences
RAS ID
28287
Grant Number
NHMRC Number : 1037321
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
Springer Nature in partnership with Australian Regenerative Medicine Institute
Comments
Salimova, E., Nowak, K. J., Estrada, A. C., Furtado, M. B., McNamara, E., Nguyen, Q., ... Rosenthal, N. A. (2019). Variable outcomes of human heart attack recapitulated in genetically diverse mice. Nature Partner Journals Regenerative Medicine, 4(1), Article 5. Available here