Variable outcomes of human heart attack recapitulated in genetically diverse mice.
Ekaterina SalimovaKristen J NowakAna C EstradaMilena B FurtadoElyshia McNamaraQuang NguyenLois BalmerChristoph PreussJeffrey W HolmesMirana RamialisonGrant MorahanNadia A RosenthalPublished in: NPJ Regenerative medicine (2019)
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.
Keyphrases
- heart failure
- genome wide
- left ventricular
- escherichia coli
- cardiovascular disease
- risk assessment
- endothelial cells
- high resolution
- copy number
- atrial fibrillation
- dna methylation
- single cell
- high glucose
- type diabetes
- drug induced
- liver failure
- heavy metals
- metabolic syndrome
- high throughput
- coronary artery disease
- human health
- gene expression
- respiratory failure
- transcription factor
- insulin resistance
- skeletal muscle
- mass spectrometry
- climate change
- protein kinase
- hepatitis b virus
- genome wide association