Using beef cattle to learn more about obesity and pulmonary hypertension in humans
By Kurt R. Stenmark and R. Dale Brown
The increased occurrence of both adult and juvenile overweight and obese individuals, termed the “obesity epidemic” in the US and other developed nations, has been accompanied by attendant increases in cardiovascular disease. The consequences of the Western diet on systemic heart disease involving the left ventricle of the heart are widely appreciated. Less well-recognized is the development of pulmonary hypertension (PH) and right ventricular dysfunction accompanying left heart disease. Classified by the World Health Organization as Group 2 PH, this is the largest and most rapidly-growing class of PH, although likely still under-reported in the general population. Right ventricular dysfunction stands as an independent predictor of mortality, and substantially worsens the prognosis for left heart disease, yet is not amenable to standardized and effective therapies developed for systemic heart disease.
Similarly to the human population, market weight and adiposity of beef cattle in commercial fattening programs using high-fat and high-carbohydrate corn-based diets in the US have increased nearly 50% over the past 50 years. Also similarly to humans, this increased size has been accompanied by an increasing incidence of congestive heart failure (CHF) in feedlot animals. We utilized veterinary diagnostic evaluation of histopathologic specimens collected at autopsy from feedlot animals with congestive heart failure, compared to matched non-symptomatic animals that completed the fattening program (we compared ten of each). Animals with CHF showed striking myocardial fibrosis, coronary artery injury, and expansion of adipose infiltrates in the left ventricle of the heart. This remodeling was accompanied by thickening and remodeling of pulmonary veins and arteries, and pathologic remodeling of the right ventricle of the heart.
Together, these findings are consistent with the syndrome of obesity-induced pulmonary hypertension and right heart dysfunction accompanying left heart disease described above. Fattening beef cattle thus provide the first naturally occurring and large animal model in order to better understand the causes, early diagnosis, and ultimate treatment of this clinically important and debilitating human disease.
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
Kurt R. Stenmark, MD is Professor of Pediatrics, Medicine, and Anesthesiology and is Head of the Division of Pediatric Critical Care Medicine and Director of the Cardiovascular Pulmonary Research Laboratory at the University of Colorado, Denver and The Children’s Hospital Colorado in Aurora, Colorado.
R. Dale Brown, PhD is Senior Instructor in the Department of Pediatrics, University of Colorado, Denver.