Murine Models of Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction

Horgan, Stephen; Watson, Courtney; Glezeva, Nadezhda; Baugh, John

doi:10.1016/j.cardfail.2014.09.001

Cited by 69 publications

(68 citation statements)

References 117 publications

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“…To our knowledge, no prior studies have demonstrated the uniqueness of basal FA composition by cell-type in the heart, or a cell-type specifi c HF that resembles some aspects of HFpEF in humans ( 20 ). Here, we sought to determine how 3-PUFA levels are correlated to these cardioprotective effects, which 3-PUFA(s) mediate prevention of fi brosis and cardiac dysfunction in this HF model, and whether prevention of cardiac dysfunction was due solely to prevention of fi brosis.…”

Section: Ffar4 Was Required To Prevent Tgf ␤ 1-induced Fi Brosis In Pmentioning

confidence: 98%

“…A limited number of studies have examined 3-PUFAs mechanistically in cell or animal models of HF. Further, due to the phenotypic variation and complicated pathophysiology of HFpEF, no animal models perfectly replicate remodeling in HFpEF ( 19,20 ). However, transverse aortic constriction (TAC), a surgical model of afterloadinduced HF, approximates some aspects of remodeling in HFpEF ( 20 ).…”

Section: Measurement Of Fi Brosismentioning

confidence: 99%

“…Further, due to the phenotypic variation and complicated pathophysiology of HFpEF, no animal models perfectly replicate remodeling in HFpEF ( 19,20 ). However, transverse aortic constriction (TAC), a surgical model of afterloadinduced HF, approximates some aspects of remodeling in HFpEF ( 20 ). TAC induces hypertrophy, interstitial cardiac fi brosis, and systolic and diastolic dysfunction, which, excluding systolic dysfunction, are common features of HFpEF.…”

Section: Measurement Of Fi Brosismentioning

confidence: 99%

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EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

Eclov

Qian

Redetzke

et al. 2015

Journal of Lipid Research

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Section: Ffar4 Was Required To Prevent Tgf ␤ 1-induced Fi Brosis In Pmentioning

confidence: 98%

Section: Measurement Of Fi Brosismentioning

confidence: 99%

Section: Measurement Of Fi Brosismentioning

confidence: 99%

See 1 more Smart Citation

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

Eclov

Qian

Redetzke

et al. 2015

Journal of Lipid Research

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“…The limited availability of animal models of HFpEF has potentially represented a major limitation in conducting mechanistic studies in the field (11). The animal models of HFpEF have hitherto involved mostly studies of increased afterload and LV hypertrophy (i.e., aortic banding or systemic arterial hypertension), models of increased preload (i.e., aorto-caval fistulas), or models of altered metabolism (i.e., obesity, diabetes, hyperlipidemia), making it difficult to distinguish between the intrinsic mechanism(s) of diastolic dysfunction vs. the mechanism(s) causing dysfunction (11).…”

Section: Chronic Infusion Of Low-dose Angiotensin II In the Mouse Indmentioning

confidence: 99%

“…The animal models of HFpEF have hitherto involved mostly studies of increased afterload and LV hypertrophy (i.e., aortic banding or systemic arterial hypertension), models of increased preload (i.e., aorto-caval fistulas), or models of altered metabolism (i.e., obesity, diabetes, hyperlipidemia), making it difficult to distinguish between the intrinsic mechanism(s) of diastolic dysfunction vs. the mechanism(s) causing dysfunction (11). Moreover, aortic banding and aorto-caval fistulas do not reflect clinically existing conditions, and the majority of patients with HFpEF continue to have HF symptoms, even when they have controlled blood pressure (BP).…”

Section: Chronic Infusion Of Low-dose Angiotensin II In the Mouse Indmentioning

confidence: 99%

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

Regan

Mauro

Carbone

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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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. Am J Physiol Heart Circ Physiol 309: H771-H778, 2015. First published July 17, 2015; doi:10.1152/ajpheart.00282.2015.-Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ϳ50% 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 (AT II) 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 AT II (0.2 mg·kg Ϫ1 ·day Ϫ1 ) or volume-matched vehicle (N ϭ 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. AT II 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 AT II recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF.heart failure with preserved ejection fraction; diastolic dysfunction; animal model; angiotensin II; end-diastolic pressure; isovolumetric relaxation time NEW & NOTEWORTHY Chronic infusion of low-dose angiotensin II in the mouse induces diastolic dysfunction and HFpEF in the absence of pressure overload, LV systolic dysfunction, LV dilatation or hypertrophy, and metabolic abnormalities. This model may be considered a novel tool for mechanistic preclinical studies in HFpEF with translational potential.HEART FAILURE (HF) WITH PRESERVED ejection fraction (HFpEF) is a clinical syndrome of symptoms of HF, such as breathlessness and exercise intolerance, associated with impaired left ventricular (LV) diastolic function in the presence of a normal LV ejection fraction (LVEF Ͼ 50%) (2). HFpEF carries significant morbidity and mortality burdens, and the prevalence of the disease has increased over the past 30 yr (2, 17). To date, the mechanisms underlying diastolic dysfunction and the progression of HFpEF are poorly understood. The path...

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Animal Models of Disease for Future Toxicity Predictions

Morgan

Elangbam

2016

Drug Discovery Toxicology

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Murine Models of Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction

Cited by 69 publications

References 117 publications

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4

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

Animal Models of Disease for Future Toxicity Predictions

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