Cardiopulmonary remodeling in fattened beef cattle: A naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease

Authors: KRAFSUR, GRETA - University Of Colorado; NEARY, JOSEPH - Texas Tech University; GARRY, FRANKLYN - Colorado State University; HOLT, TIMOTHY - Colorado State University; GOULD, DANIEL - Colorado State University; MASON, GARY - Colorado State University; THOMAS, MILTON - Colorado State University; ENNS, R - Colorado State University; TUDER, RUBIN - University Of Colorado; Heaton, Michael - Mike; BROWN, R - University Of Colorado; STENMARK, KURT - University Of Colorado

Submitted to: Pulmonary Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2018
Publication Date: 1/10/2019
Citation: Krafsur, G.M., Neary, J.M., Garry, F., Holt, T., Gould, D.H., Mason, G.L., Thomas, M.G., Enns, R.M., Tuder, R.M., Heaton, M.P., Brown, R.D., Stenmark, K.R. 2019. Cardiopulmonary remodeling in fattened beef cattle: A naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease. Pulmonary Circulation. 9(1):1-13. https://doi.org/10.1177/2045894018796804.
DOI: https://doi.org/10.1177/2045894018796804

Interpretive Summary: The global obesity epidemic in industrialized societies and developing countries has led to increased cardiovascular diseases, including pulmonary hypertension associated with heart failure. Similar to obese humans, the same disorder is increasingly recognized in North American cattle fattened for beef processing. We hypothesized that the pulmonary hypertension and heart failure observed in fattened cattle are similar to that observed in obese humans. We conducted a study of tissues from fattened beef cattle experiencing endstage heart failure and compared them to apparently healthy cattle of equivalent age undergoing the same feeding regimens. In animals with heart failure, there were significant signs of left-sided heart disease similar to those in obese humans suffering from the same disease. This novel, naturally occurring and large animal model may provide mechanistic and translational insights into human disease.

Technical Abstract: 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 semiquantitative histopathological assessment of cardiopulmonary tissues obtained from fattened beef cattle suffering endstage 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.