Variable outcomes of human heart attack recapitulated in genetically diverse mice

Ekaterina Salimova, Kristen J. Nowak, Ana C. Estrada, Milena B. Furtado, Elyshia McNamara, Quang Nguyen, Lois Balmer, Christoph Preuss, Jeffrey W. Holmes, Mirana Ramialison, Grant Morahan, Nadia A. Rosenthal

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Article number5
Number of pages15
JournalNpj Regenerative Medicine
Volume4
DOIs
Publication statusPublished - 4 Mar 2019

Keywords

  • genetic predisposition to disease
  • translational research

Cite this

Salimova, Ekaterina ; Nowak, Kristen J. ; Estrada, Ana C. ; Furtado, Milena B. ; McNamara, Elyshia ; Nguyen, Quang ; Balmer, Lois ; Preuss, Christoph ; Holmes, Jeffrey W. ; Ramialison, Mirana ; Morahan, Grant ; Rosenthal, Nadia A. / Variable outcomes of human heart attack recapitulated in genetically diverse mice. In: Npj Regenerative Medicine. 2019 ; Vol. 4.
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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.",
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Variable outcomes of human heart attack recapitulated in genetically diverse mice. / Salimova, Ekaterina; Nowak, Kristen J.; Estrada, Ana C.; Furtado, Milena B.; McNamara, Elyshia; Nguyen, Quang; Balmer, Lois; Preuss, Christoph; Holmes, Jeffrey W.; Ramialison, Mirana; Morahan, Grant; Rosenthal, Nadia A.

In: Npj Regenerative Medicine, Vol. 4, 5, 04.03.2019.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Variable outcomes of human heart attack recapitulated in genetically diverse mice

AU - Salimova, Ekaterina

AU - Nowak, Kristen J.

AU - Estrada, Ana C.

AU - Furtado, Milena B.

AU - McNamara, Elyshia

AU - Nguyen, Quang

AU - Balmer, Lois

AU - Preuss, Christoph

AU - Holmes, Jeffrey W.

AU - Ramialison, Mirana

AU - Morahan, Grant

AU - Rosenthal, Nadia A.

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AB - 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.

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