Abstract
Patients with left ventricle (LV) volume overload (VO) remain in a compensated state for many years although severe dilation is present. The myocardial capacity to fulfill its energetic demand may delay decompensation. We performed a gene expression profile, a model of chronic VO in rat LV with severe aortic valve regurgitation (AR) for 9 months, and focused on the study of genes associated with myocardial energetics. Methods. LV gene expression profile was performed in rats after 9 months of AR and compared to sham-operated controls. LV glucose and fatty acid (FA) uptake was also evaluated in vivo by positron emission tomography in 8-week AR rats treated or not with fenofibrate, an activator of FA oxidation (FAO). Results. Many LV genes associated with mitochondrial function and metabolism were downregulated in AR rats. FA β-oxidation capacity was significantly impaired as early as two weeks after AR. Treatment with fenofibrate, a PPARα agonist, normalized both FA and glucose uptake while reducing LV dilation caused by AR. Conclusion. Myocardial energy substrate preference is affected early in the evolution of LV-VO cardiomyopathy. Maintaining a relatively normal FA utilization in the myocardium could translate into less glucose uptake and possibly lesser LV remodeling.
Highlights
Aortic regurgitation (AR) is associated with a long asymptomatic period during which the left ventricle (LV) progressively dilates and hypertrophies in response to chronic volume overload
Gene expression profiles have been established in several animal models of LV eccentric hypertrophy, including by us in a rat model after two weeks of severe AR, a period characterized with intense LV remodeling [5,6,7,8]
We show a general downregulation of genes involved in fatty acid oxidation and bioenergetics
Summary
Aortic regurgitation (AR) is associated with a long asymptomatic period during which the left ventricle (LV) progressively dilates and hypertrophies in response to chronic volume overload. This process is accompanied by a decrease in LV function, occurrence of symptoms, and eventually heart failure [1]. Contrary to the fast evolution of other VO models such as aortocaval fistula (ACF), severe AR in rats is associated with important LV hypertrophy and dilation, moderate loss of systolic function, diastolic dysfunction, and a low rate of congestive heart failure [9,10,11].
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