Variable phenotype in murine transverse aortic constriction

Selma F. Mohammed, Jimmy R. Storlie, Elise A. Oehler, Lorna A. Bowen, Josef Korinek, Carolyn S P Lam, Robert D. Simari, John C Jr. Burnett, Margaret May Redfield

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Methods: Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice. Results: As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC. Conclusions: In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalCardiovascular Pathology
Volume21
Issue number3
DOIs
StatePublished - May 2012

Fingerprint

Constriction
Phenotype
Heart Failure
Echocardiography
Aorta
Blood Pressure
Stroke Volume
Weights and Measures
Left Ventricular Hypertrophy
Ventricular Pressure
Inbred C57BL Mouse
Hypertrophy
Autopsy
Arterial Pressure

Keywords

  • Cardiac geometry
  • Left ventricular hypertrophy (LVH)
  • Murine models
  • Pressure overload hypertrophy
  • Transverse aortic constriction (TAC)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pathology and Forensic Medicine

Cite this

Mohammed, S. F., Storlie, J. R., Oehler, E. A., Bowen, L. A., Korinek, J., Lam, C. S. P., ... Redfield, M. M. (2012). Variable phenotype in murine transverse aortic constriction. Cardiovascular Pathology, 21(3), 188-198. https://doi.org/10.1016/j.carpath.2011.05.002

Variable phenotype in murine transverse aortic constriction. / Mohammed, Selma F.; Storlie, Jimmy R.; Oehler, Elise A.; Bowen, Lorna A.; Korinek, Josef; Lam, Carolyn S P; Simari, Robert D.; Burnett, John C Jr.; Redfield, Margaret May.

In: Cardiovascular Pathology, Vol. 21, No. 3, 05.2012, p. 188-198.

Research output: Contribution to journalArticle

Mohammed, SF, Storlie, JR, Oehler, EA, Bowen, LA, Korinek, J, Lam, CSP, Simari, RD, Burnett, JCJ & Redfield, MM 2012, 'Variable phenotype in murine transverse aortic constriction', Cardiovascular Pathology, vol. 21, no. 3, pp. 188-198. https://doi.org/10.1016/j.carpath.2011.05.002
Mohammed SF, Storlie JR, Oehler EA, Bowen LA, Korinek J, Lam CSP et al. Variable phenotype in murine transverse aortic constriction. Cardiovascular Pathology. 2012 May;21(3):188-198. https://doi.org/10.1016/j.carpath.2011.05.002
Mohammed, Selma F. ; Storlie, Jimmy R. ; Oehler, Elise A. ; Bowen, Lorna A. ; Korinek, Josef ; Lam, Carolyn S P ; Simari, Robert D. ; Burnett, John C Jr. ; Redfield, Margaret May. / Variable phenotype in murine transverse aortic constriction. In: Cardiovascular Pathology. 2012 ; Vol. 21, No. 3. pp. 188-198.
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abstract = "Background: In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC. Methods: Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice. Results: As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28{\%}) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC. Conclusions: In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies.",
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