4.6 Article

Novel Gottingen Miniswine Model of Heart Failure With Preserved Ejection Fraction Integrating Multiple Comorbidities

Journal

JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 6, Issue 2, Pages 154-170

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2020.11.012

Keywords

animal models of human disease; obesity; metabolic syndrome; hypertension; heart failure with preserved ejection fraction

Funding

  1. National Institutes of Health [R01 HL128349, R01 HL151345, 1R01 HL146098, 1R56HL137711, 1R01 HL146514, 1R01 HL151398]
  2. National Institute of Health [T32HL007843]

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This study developed a novel large animal model of HFpEF that replicates the multiple comorbidities associated with human HFpEF, providing a valuable tool for investigating the pathogenesis of the disease and testing new therapeutic strategies.
A lack of preclinical large animal models of heart failure with preserved ejection fraction (HFpEF) that recapitulate this comorbid-laden syndrome has led to the inability to tease out mechanistic insights and to test novel therapeutic strategies. This study developed a large animal model that integrated multiple comorbid determinants of HFpEF in a miniswine breed that exhibited sensitivity to obesity, metabolic syndrome, and vascular disease with overt clinical signs of heart failure. The combination of a Western diet and 11-deoxycorticosterone acetate salt-induced hypertension in the Gottingen miniswine led to the development of a novel large animal model of HFpEF that exhibited multiorgan involvement and a full spectrum of comorbidities associated with human HFpEF. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

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