In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart

Michael S. Dodd, Daniel R. Ball, Marie A. Schroeder, Lydia M. Le Page, Helen J. Atherton, Lisa C. Heather, Anne Marie Seymour, Houman Ashrafian, Hugh Watkins, Kieran Clarke, Damian J. Tyler

Research output: Contribution to journalArticle

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Abstract

Aims The aim of this work was to use hyperpolarized carbon-13 ( 13C) magnetic resonance (MR) spectroscopy and cine MR imaging (MRI) to assess in vivo cardiac metabolism and function in the 15-week-old spontaneously hypertensive rat (SHR) heart. At this time point, the SHR displays hypertension and concentric hypertrophy. One of the cellular adaptations to hypertrophy is a reduction in β-oxidation, and it has previously been shown that in response to hypertrophy the SHR heart switches to a glycolytic/glucose-oxidative phenotype. Methods and results Cine-MRI (magnetic resonance imaging) was used to assess cardiac function and degree of cardiac hypertrophy. Wistar rats were used as controls. SHRs displayed functional changes in stroke volume, heart rate, and late peak-diastolic filling alongside significant hypertrophy (a 56 increase in left ventricular mass). Using hyperpolarized [1- 13C] and [2- 13C]pyruvate, an 85 increase in 13C label flux through pyruvate dehydrogenase (PDH) was seen in the SHR heart and 13C label incorporation into citrate, acetylcarnitine, and glutamate pools was elevated in proportion to the increase in PDH flux. These findings were confirmed using biochemical analysis of PDH activity and protein expression of PDH regulatory enzymes. Conclusion sFunctional and structural alterations in the SHR heart are consistent with the hypertrophied phenotype. Our in vivo work indicates a preference for glucose metabolism in the SHR heart, a move away from predominantly fatty acid oxidative metabolism. Interestingly, 13C label flux into lactate was unchanged, indicating no switch to an anaerobic glycolytic phenotype, but rather an increased reliance on glucose oxidation in the SHR heart. Published on behalf of the European Society of Cardiology. All rights reserved.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalCardiovascular Research
Volume95
Issue number1
DOIs
Publication statusPublished - 1 Jul 2012
Externally publishedYes

Fingerprint

Inbred SHR Rats
Pyruvic Acid
Hypertrophy
Oxidoreductases
Phenotype
Glucose
Cine Magnetic Resonance Imaging
Acetylcarnitine
Cardiomegaly
Citric Acid
Stroke Volume
Wistar Rats
Glutamic Acid
Lactic Acid
Fatty Acids
Heart Rate
Magnetic Resonance Imaging
Hypertension
Enzymes
Proteins

Keywords

  • Carbon-13 Magnetic resonance spectroscopy
  • Dynamic nuclear polarization
  • Metabolism
  • Pyruvate dehydrogenase
  • Spontaneously hypertensive rat

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Dodd, M. S., Ball, D. R., Schroeder, M. A., Le Page, L. M., Atherton, H. J., Heather, L. C., ... Tyler, D. J. (2012). In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart. Cardiovascular Research, 95(1), 69-76. https://doi.org/10.1093/cvr/cvs164

In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart. / Dodd, Michael S.; Ball, Daniel R.; Schroeder, Marie A.; Le Page, Lydia M.; Atherton, Helen J.; Heather, Lisa C.; Seymour, Anne Marie; Ashrafian, Houman; Watkins, Hugh; Clarke, Kieran; Tyler, Damian J.

In: Cardiovascular Research, Vol. 95, No. 1, 01.07.2012, p. 69-76.

Research output: Contribution to journalArticle

Dodd, MS, Ball, DR, Schroeder, MA, Le Page, LM, Atherton, HJ, Heather, LC, Seymour, AM, Ashrafian, H, Watkins, H, Clarke, K & Tyler, DJ 2012, 'In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart' Cardiovascular Research, vol. 95, no. 1, pp. 69-76. https://doi.org/10.1093/cvr/cvs164
Dodd, Michael S. ; Ball, Daniel R. ; Schroeder, Marie A. ; Le Page, Lydia M. ; Atherton, Helen J. ; Heather, Lisa C. ; Seymour, Anne Marie ; Ashrafian, Houman ; Watkins, Hugh ; Clarke, Kieran ; Tyler, Damian J. / In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart. In: Cardiovascular Research. 2012 ; Vol. 95, No. 1. pp. 69-76.
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AU - Ball, Daniel R.

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AU - Atherton, Helen J.

AU - Heather, Lisa C.

AU - Seymour, Anne Marie

AU - Ashrafian, Houman

AU - Watkins, Hugh

AU - Clarke, Kieran

AU - Tyler, Damian J.

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N2 - Aims The aim of this work was to use hyperpolarized carbon-13 ( 13C) magnetic resonance (MR) spectroscopy and cine MR imaging (MRI) to assess in vivo cardiac metabolism and function in the 15-week-old spontaneously hypertensive rat (SHR) heart. At this time point, the SHR displays hypertension and concentric hypertrophy. One of the cellular adaptations to hypertrophy is a reduction in β-oxidation, and it has previously been shown that in response to hypertrophy the SHR heart switches to a glycolytic/glucose-oxidative phenotype. Methods and results Cine-MRI (magnetic resonance imaging) was used to assess cardiac function and degree of cardiac hypertrophy. Wistar rats were used as controls. SHRs displayed functional changes in stroke volume, heart rate, and late peak-diastolic filling alongside significant hypertrophy (a 56 increase in left ventricular mass). Using hyperpolarized [1- 13C] and [2- 13C]pyruvate, an 85 increase in 13C label flux through pyruvate dehydrogenase (PDH) was seen in the SHR heart and 13C label incorporation into citrate, acetylcarnitine, and glutamate pools was elevated in proportion to the increase in PDH flux. These findings were confirmed using biochemical analysis of PDH activity and protein expression of PDH regulatory enzymes. Conclusion sFunctional and structural alterations in the SHR heart are consistent with the hypertrophied phenotype. Our in vivo work indicates a preference for glucose metabolism in the SHR heart, a move away from predominantly fatty acid oxidative metabolism. Interestingly, 13C label flux into lactate was unchanged, indicating no switch to an anaerobic glycolytic phenotype, but rather an increased reliance on glucose oxidation in the SHR heart. Published on behalf of the European Society of Cardiology. All rights reserved.

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