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A2093 - Effects of Carbohydrate Metabolism on Development of Pulmonary Hypertension
Author Block: L. R. Villegas, J. Yates, J. H. Chun, H. Austin, B. Ramos, A. Hanson, D. Pokhrel, C. King, M. T. Le; University of Colorado, Anschutz Medical Campus, Aurora, CO, United States.
Rationale: Sugar consumption in the western diet has risen drastically, parallel to a dramatic increase in diabetes, metabolic syndrome, obesity and cardiovascular disease. Although studies have shown that the excessive consumption of sugars, especially fructose, can induce inflammation and promote abnormal vascular responses and systemic hypertension, the impact of sugar metabolism on the pulmonary vasculature has not yet been studied. The objective of our studies is to develop a rodent model to investigate the effects of sugar dysmetabolism on the development of pulmonary hypertension. We hypothesize that increased consumption of carbohydrates, especially fructose, induces inflammatory pathways that lead to vascular remodeling and development of pulmonary hypertension, and that adverse effects are affected by age.
Methods: Studies were performed in the following rodent species/strains: C57/BL6 wild type and NLRP3 knockout male mice (age range from 1 to 9 months) and Sprague Dawley rats (age range from 1 to 7 months). Rodents were fed normal chow and given 30% sucrose, 15% sucrose or 15% fructose in drinking water (controls received normal water) ad libitum for up to 12 weeks. The amount of water and chow consumed was monitored to account for total caloric intake. Body weight was also monitored. Pulmonary artery and systemic pressures were measured using fluid filled catheters and pressure transducer. Blood chemistry was measured and tissue histology assessed to evaluate tissue injury, inflammation, and vascular remodeling.
Results: Rodents receiving 15% sucrose or 15% fructose consumed more sugar water but less chow. While all sugar-fed animals had increased blood glucose levels, the younger rodents did not show difference in body weight gain, cholesterol, triglycerides, or systemic blood pressure relative to controls yet had increased epididymal fat, liver injury, pulmonary artery pressure and right heart abnormality. Preliminary evidence show that increased sugar intake may mediate inflammatory pathways such as inflammasome and mast cell recruitment to the lungs, and pulmonary vascular remodeling. The older rodents receiving high sugar diets had significant weight gain compared to controls and also began to present with abnormal blood chemistry, fat accumulation, and injury in the liver, lungs and right heart.
Conclusions: These studies contribute to the advancement in our understanding of how sugar overconsumption and dysmetabolism impact pulmonary vascular pathophysiology. Our studies suggest that, in younger populations, sugar dysmetabolism may begin to exert its effects on the pulmonary circulation before outward signs such as weight gain and systemic hypertension that are evident in older populations.