Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease
The obesity epidemic in developed societies has led to increased cardiovascular diseases including pulmonary hypertension associated with left heart disease (PH-LHD), the largest and fastest-growing class of PH. Similar to obese humans, PH and heart failure (HF) are increasingly recognized in North...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/2045894018796804 |
| _version_ | 1811228335138668544 |
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| author | Greta M. Krafsur Joseph M. Neary Franklyn Garry Timothy Holt Daniel H. Gould Gary L. Mason Milton G. Thomas R. Mark Enns Rubin M. Tuder Michael P. Heaton R. Dale Brown Kurt R. Stenmark |
| author_facet | Greta M. Krafsur Joseph M. Neary Franklyn Garry Timothy Holt Daniel H. Gould Gary L. Mason Milton G. Thomas R. Mark Enns Rubin M. Tuder Michael P. Heaton R. Dale Brown Kurt R. Stenmark |
| author_sort | Greta M. Krafsur |
| collection | DOAJ |
| description | The obesity epidemic in developed societies has led to increased cardiovascular diseases including pulmonary hypertension associated with left heart disease (PH-LHD), the largest and fastest-growing class of PH. Similar to obese humans, PH and heart failure (HF) are increasingly recognized in North American fattened beef cattle. We hypothesized that PH and HF in fattened beef cattle are novel, phenotypically distinct manifestations of bovine PH arising from left ventricular (LV) dysfunction similar to obesity-related PH-LHD in humans. We conducted a semi-quantitative histopathological assessment of cardiopulmonary tissues obtained from fattened beef cattle suffering end-stage HF compared to asymptomatic cattle of equivalent age undergoing the same fattening regimens. In HF animals we observed significant LV fibrosis, abundant cardiac adipose depots, coronary artery injury, and pulmonary venous remodeling recapitulating human obesity-related PH-LHD. Additionally, striking muscularization, medial hypertrophy, adventitial fibrosis, and vasa vasorum hyperplasia in the pulmonary arterial circulation were associated with sequela of pathologic right ventricular (RV) remodeling suggesting combined pulmonary venous and arterial hypertension. The association between obesity, pathologic cardiopulmonary remodeling, and HF in fattened beef cattle appears to recapitulate the complex pathophysiology of obesity-associated PH-LHD in humans. This novel, naturally occurring, and large animal model may provide mechanistic and translational insights into human disease. |
| first_indexed | 2024-04-12T09:56:14Z |
| format | Article |
| id | doaj.art-440dfeb8daf044be9bebb2ecdcdb36eb |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-04-12T09:56:14Z |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-440dfeb8daf044be9bebb2ecdcdb36eb2022-12-22T03:37:40ZengWileyPulmonary Circulation2045-89402019-01-01910.1177/2045894018796804Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart diseaseGreta M. Krafsur0Joseph M. Neary1Franklyn Garry2Timothy Holt3Daniel H. Gould4Gary L. Mason5Milton G. Thomas6R. Mark Enns7Rubin M. Tuder8Michael P. Heaton9R. Dale Brown10Kurt R. Stenmark11Department of Animal Sciences, Colorado State University, Fort Collins, CO, USADepartment of Animal and Food Sciences, Texas Tech University, Lubbock, TX, USADepartment of Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO, USADepartment of Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO, USADepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USADepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USADepartment of Animal Sciences, Colorado State University, Fort Collins, CO, USADepartment of Animal Sciences, Colorado State University, Fort Collins, CO, USADepartment of Pulmonary Sciences and Critical Care Medicine, Translational Lung Program, University of Colorado Denver Anschutz School of Medicine, Aurora, CO, USAGenetics, Breeding and Animal Health, United States Meat Animal Research Center, Clay Center, NE, USADepartment of Pediatrics, Critical Care Medicine and Cardiovascular Pulmonary Research Labs, University of Colorado Denver Anschutz School of Medicine, Aurora, CO, USADepartment of Pediatrics, Critical Care Medicine and Cardiovascular Pulmonary Research Labs, University of Colorado Denver Anschutz School of Medicine, Aurora, CO, USAThe obesity epidemic in developed societies has led to increased cardiovascular diseases including pulmonary hypertension associated with left heart disease (PH-LHD), the largest and fastest-growing class of PH. Similar to obese humans, PH and heart failure (HF) are increasingly recognized in North American fattened beef cattle. We hypothesized that PH and HF in fattened beef cattle are novel, phenotypically distinct manifestations of bovine PH arising from left ventricular (LV) dysfunction similar to obesity-related PH-LHD in humans. We conducted a semi-quantitative histopathological assessment of cardiopulmonary tissues obtained from fattened beef cattle suffering end-stage HF compared to asymptomatic cattle of equivalent age undergoing the same fattening regimens. In HF animals we observed significant LV fibrosis, abundant cardiac adipose depots, coronary artery injury, and pulmonary venous remodeling recapitulating human obesity-related PH-LHD. Additionally, striking muscularization, medial hypertrophy, adventitial fibrosis, and vasa vasorum hyperplasia in the pulmonary arterial circulation were associated with sequela of pathologic right ventricular (RV) remodeling suggesting combined pulmonary venous and arterial hypertension. The association between obesity, pathologic cardiopulmonary remodeling, and HF in fattened beef cattle appears to recapitulate the complex pathophysiology of obesity-associated PH-LHD in humans. This novel, naturally occurring, and large animal model may provide mechanistic and translational insights into human disease.https://doi.org/10.1177/2045894018796804 |
| spellingShingle | Greta M. Krafsur Joseph M. Neary Franklyn Garry Timothy Holt Daniel H. Gould Gary L. Mason Milton G. Thomas R. Mark Enns Rubin M. Tuder Michael P. Heaton R. Dale Brown Kurt R. Stenmark Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease Pulmonary Circulation |
| title | Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease |
| title_full | Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease |
| title_fullStr | Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease |
| title_full_unstemmed | Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease |
| title_short | Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease |
| title_sort | cardiopulmonary remodeling in fattened beef cattle a naturally occurring large animal model of obesity associated pulmonary hypertension with left heart disease |
| url | https://doi.org/10.1177/2045894018796804 |
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