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      Understanding HFpEF With Obesity : Will Pigs Come to the Rescue? ∗

      editorial
      Author(s): , MD ∗
      Publication date (Electronic):
      Journal: JACC: Basic to Translational Science
      Publisher: Elsevier
      Keywords: animal models, diastolic heart failure, ejection fraction, heart failure, metabolic syndrome, obesity

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          A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.

          Michael Schwarzl, Nazha Hamdani, Sebastian Seiler … (2015)
          Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.
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            Western diet-fed, aortic-banded ossabaw swine: a preclinical model of cardio-metabolic heart failure

            T Olver, J Edwards, T. Jurrissen … (2019)
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              Obesity-Related heart failure with preserved ejection fraction: pathophysiology, diagnosis and potential therapies

              T HARADA, M. Obokata (2020)
              Article 0 comments Cited 2 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                David A. Kass: @dkassjhu
                Journal
                Journal ID (nlm-ta): JACC Basic Transl Sci
                Journal ID (iso-abbrev): JACC Basic Transl Sci
                Title: JACC: Basic to Translational Science
                Publisher: Elsevier
                ISSN (Electronic): 2452-302X
                Publication date PMC-release: 22 February 2021
                Publication date Collection: February 2021
                Publication date (Electronic): 22 February 2021
                Volume: 6
                Issue: 2
                Pages: 171-173
                Affiliations
                [1]Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
                Author notes
                [∗ ] Address for correspondence: Dr. David A. Kass, Division of Cardiology, Johns Hopkins University School of Medicine, Ross Research Building, Room 858, 720 Rutland Avenue, Baltimore, Maryland 21205, USA. dkass@ 123456jhmi.edu @dkassjhu
                [∗]

                Editorials published in JACC: Basic to Translational Science reflect the views of the authors and do not necessarily represent the views of JACC: Basic to Translational Science or the American College of Cardiology.

                Article
                Publisher Item ID: S2452-302X(20)30549-0
                DOI: 10.1016/j.jacbts.2020.12.010
                PMC ID: 7907620
                PubMed ID: 33688854
                SO-VID: 321f9392-89db-4e07-a567-352a35c98ac4
                Copyright © © 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Subject: Editorial Comment

                Keywords: animal models,diastolic heart failure,ejection fraction,heart failure,metabolic syndrome,obesity
                Data availability:
                Keywords: animal models, diastolic heart failure, ejection fraction, heart failure, metabolic syndrome, obesity

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