Transcriptional Changes Associated with Long-Term Left Ventricle Volume Overload in Rats: Impact on Enzymes Related to Myocardial Energy Metabolism

Abstract EN

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.