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A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II.

Publication ,  Journal Article
Regan, JA; Mauro, AG; Carbone, S; Marchetti, C; Gill, R; Mezzaroma, E; Valle Raleigh, J; Salloum, FN; Van Tassell, BW; Abbate, A; Toldo, S
Published in: American journal of physiology. Heart and circulatory physiology
September 2015

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg(-1)·day(-1)) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF.

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Published In

American journal of physiology. Heart and circulatory physiology

DOI

EISSN

1522-1539

ISSN

0363-6135

Publication Date

September 2015

Volume

309

Issue

5

Start / End Page

H771 / H778

Related Subject Headings

  • Stroke Volume
  • Mice
  • Male
  • Infusions, Subcutaneous
  • Heart Failure
  • Disease Models, Animal
  • Cardiovascular System & Hematology
  • Blood Pressure
  • Animals
  • Angiotensin II
 

Citation

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Regan, J. A., Mauro, A. G., Carbone, S., Marchetti, C., Gill, R., Mezzaroma, E., … Toldo, S. (2015). A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II. American Journal of Physiology. Heart and Circulatory Physiology, 309(5), H771–H778. https://doi.org/10.1152/ajpheart.00282.2015
Regan, Jessica A., Adolfo Gabriele Mauro, Salvatore Carbone, Carlo Marchetti, Rabia Gill, Eleonora Mezzaroma, Juan Valle Raleigh, et al. “A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II.American Journal of Physiology. Heart and Circulatory Physiology 309, no. 5 (September 2015): H771–78. https://doi.org/10.1152/ajpheart.00282.2015.
Regan JA, Mauro AG, Carbone S, Marchetti C, Gill R, Mezzaroma E, et al. A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II. American journal of physiology Heart and circulatory physiology. 2015 Sep;309(5):H771–8.
Regan, Jessica A., et al. “A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II.American Journal of Physiology. Heart and Circulatory Physiology, vol. 309, no. 5, Sept. 2015, pp. H771–78. Epmc, doi:10.1152/ajpheart.00282.2015.
Regan JA, Mauro AG, Carbone S, Marchetti C, Gill R, Mezzaroma E, Valle Raleigh J, Salloum FN, Van Tassell BW, Abbate A, Toldo S. A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II. American journal of physiology Heart and circulatory physiology. 2015 Sep;309(5):H771–H778.

Published In

American journal of physiology. Heart and circulatory physiology

DOI

EISSN

1522-1539

ISSN

0363-6135

Publication Date

September 2015

Volume

309

Issue

5

Start / End Page

H771 / H778

Related Subject Headings

  • Stroke Volume
  • Mice
  • Male
  • Infusions, Subcutaneous
  • Heart Failure
  • Disease Models, Animal
  • Cardiovascular System & Hematology
  • Blood Pressure
  • Animals
  • Angiotensin II