Both male and female obese ZSF1 rats develop cardiac dysfunction in obesity-induced heart failure with preserved ejection fraction.

Autor: Nguyen ITN; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands., Brandt MM; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., van de Wouw J; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., van Drie RWA; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Wesseling M; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Cramer MJ; Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands., de Jager SCA; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Merkus D; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Walter Brendel Center of Experimental Medicine (WBex), Munich, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany., Duncker DJ; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Cheng C; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.; Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Joles JA; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands., Verhaar MC; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 May 06; Vol. 15 (5), pp. e0232399. Date of Electronic Publication: 2020 May 06 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0232399
Abstrakt: Heart failure with a preserved ejection fraction (HFpEF) is associated with multiple comorbidities, such as old age, hypertension, type 2 diabetes and obesity and is more prevalent in females. Although the male obese ZSF1 rat has been proposed as a suitable model to study the development of diastolic dysfunction and early HFpEF, studies in female animals have not been performed yet. Therefore, we aimed to characterize the cardiac phenotype in female obese ZSF1 rats and their lean counterparts. Additionally, we aimed to investigate whether differences exist in disease progression in obese male and female ZSF1 rats. Therefore, male and female ZSF1 rats, lean as well as obese (N = 6-9/subgroup), were used. Every two weeks, from 12 to 26 weeks of age, systolic blood pressure and echocardiographic measurements were performed, and venous blood was sampled. Female obese ZSF1 rats, as compared to female lean ZSF1 rats, developed diastolic dysfunction with cardiac hypertrophy and fibrosis in the presence of severe dyslipidemia, increased plasma growth differentiation factor 15 and mild hypertension, and preservation of systolic function. Although obese female ZSF1 rats did not develop hyperglycemia, their diastolic dysfunction was as severe as in the obese males. Taken together, the results from the present study suggest that the female obese ZSF1 rat is a relevant animal model for HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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