Author + information
- Received January 17, 2019
- Revision received February 13, 2019
- Accepted February 21, 2019
- Published online June 24, 2019.
- T. Dylan Olver, PhDa,∗,
- Jenna C. Edwards, BSa,∗,
- Thomas J. Jurrissen, BSb,
- Adam B. Veteto, MSc,
- John L. Jones, MSc,
- Chen Gao, BSd,
- Christoph Rau, PhDd,
- Chad M. Warren, MSe,
- Paula J. Klutho, PhDf,
- Linda Alex, PhDf,
- Stephanie C. Ferreira-Nichols, BSf,
- Jan R. Ivey, BSa,
- Pamela K. Thorne, MSa,
- Kerry S. McDonald, PhDc,
- Maike Krenz, MDc,f,
- Christopher P. Baines, PhDa,c,f,
- R. John Solaro, PhDe,
- Yibin Wang, PhDd,
- David A. Ford, PhDg,
- Timothy L. Domeier, PhDc,†∗ (, )
- Jaume Padilla, PhDb,f,i,†∗ (, )
- R. Scott Rector, PhDb,h,j,†∗ ( and )
- Craig A. Emter, PhDa,†∗ ()
- aDepartment of Biomedical Science, University of Missouri-Columbia, Columbia, Missouri
- bDepartment of Nutrition and Exercise Physiology, University of Missouri-Columbia, Columbia, Missouri
- cDepartment of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri
- dDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
- eDepartment of Physiology and Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois
- fDalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri
- gDepartment of Biochemistry and Molecular Biology and Center for Cardiovascular Research, Saint Louis University- School of Medicine, St. Louis, Missouri
- hDepartment of Medicine – University of Missouri-Columbia, Columbia, Missouri
- iDepartment of Child Health, University of Missouri-Columbia, Columbia, Missouri
- jResearch Service, Harry S Truman Memorial VA Hospital, University of Missouri-Columbia, Columbia, Missouri
- ↵∗Address for correspondence:
Dr. Craig A. Emter, Dr. R. Scott Rector, Dr. Jaume Padilla, and Dr. Timothy L. Domeier, University of Missouri-Columbia, 1600 East Rollins, Columbia, Missouri 65211.
• The combination of a Western-diet and aortic banding results in a cardio-metabolic heart failure phenotype in Ossabaw swine.
• Ossabaw swine with cardio-metabolic heart failure display cardiac dysfunction at the whole heart and cellular levels.
• The left ventricle transcriptome showed gene signatures consistent with pro-inflammatory heart failure.
• Cardio-metabolic heart failure was coupled with microvascular dysfunction in the heart, skeletal muscle, and brain.
• Ossabaw swine with cardio-metabolic heart failure are sedentary and obese with liver dysfunction.
The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet−fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF.
- cardio-metabolic disease
- heart failure
- integrative pathophysiology
- preclinical model of cardiovascular disease
↵∗ Dr. Oliver and Ms. Edwards contributed equally to this work and are joint first authors.
↵† Drs. Domeier, Padilla, Rector, and Emter contributed equally to this work and are joint senior authors.
This study was supported by a University of Missouri Research Board Grant (principal investigators [PIs]: Drs. Emter and Rector); National Institutes of Health (NIH) Grant RO1 HL112998 (PI: Dr. Emter); VA-Merit Grant I01BX003271-01 (PI: Dr. Rector); NIH Grant K01 HL125503 (PI: Dr. Padilla); NIH Grant K01 AG041208 and R01 HL136292 (PI: Dr. Domeier); American Heart Association postdoctoral fellowship 16POST27760052 (PI: Dr. Olver); NIH Grant R01 HL094404 (PI: Dr. Baines); NIH Grant R01 GM115552 (PI: Dr. Ford); NIH Grants R01 HL122737, NIH R01 HL123295, and NIH HL129639 (PI: Dr. Wang); American Heart Association postdoctoral fellowship 17POST33661136 (PI: Dr. Gao); NIH Grant R01 HL116525 (PI: Krenz); and NIH Grant PO1 HL62426 (Project 1, Dr. Solaro; Core C: Dr. Warren). The authors acknowledge NIH grants RR013223 and HL062552 to M. Sturek and the CMP of IUSM and Purdue University, and NIH grant U42 OD011140 to R. Prather and the National Swine Resource and Research Center at the University of Missouri-Columbia for the Ossabaw swine. Dr. Solaro has served on the Scientific Advisory Board and been a consultant for Cytokinetics; and has a fee-for-service agreement with Pfizer. Dr. Wang has been a consultant for REMD Biotherapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received January 17, 2019.
- Revision received February 13, 2019.
- Accepted February 21, 2019.
- 2019 The Authors