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Transgenic Rat Model Overexpressing Endothelial β 3 ‐adrenoceptor: a New Model for Heart Failure with Preserved Ejection Fraction
Author(s) -
Prat Valentine,
Roul David,
Ferron Marine,
Piriou Nicolas,
Guijarro Damien,
Grabherr Amandine,
Aillerie Virginie,
Erraud Angélique,
Lauzier Benjamin,
Rozec Bertrand,
Gauthier Chantal
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.799.2
Subject(s) - preload , heart failure , ejection fraction , ventricle , medicine , contractility , cardiology , heart failure with preserved ejection fraction , diastole , context (archaeology) , fibrosis , diastolic heart failure , pathophysiology , genetically modified mouse , endocrinology , transgene , blood pressure , hemodynamics , chemistry , biology , paleontology , biochemistry , gene
Heart failure (HF) with preserved ejection fraction (pEF) is a growing health burden affecting the elderly. Patients classically express impaired cardiac relaxation and filling. Due to the lack of patient biopsies and accurate animal models, its physiopathology remains unclear and no specific treatment is currently available. In this context, our team developed a transgenic rat model (Tgβ 3 ) overexpressing human β 3 ‐adrenoceptor at endothelial level. At 45 weeks of age, males presented an increase in left ventricle end diastolic pressure (LVEDP; WT: 5.6±1.2; Tgβ 3 : 11.7±1.1; p<0.01) and dP/dt max , a contractility parameter (WT: 6333±370; Tgβ 3 : 7808±191; p<0.01), characteristic of an increase in LV stiffness and in peripheral resistances. Echographic study showed an altered filling pattern with an increase in early‐to‐late filling (E/A) ratio (WT:1.14±0.01; Tgβ 3 : 1.32±0.04; p<0.01), with a pEF but without macroscopic cardiac remodeling. These results showed that Tgβ 3 rats presented a restrictive cardiac filling, representative of the HFpEF phenotype. Further studies, such as fibrosis quantification and calcium cycle study, are needed to determine the underlying mechanisms of the diastolic impairment, as well as to identify molecular targets altered in this disease in order to develop a new therapeutic strategy for HFpEF treatment.