Activation of PPAR-{alpha} in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure

We examined the effect of PPAR-α induction during heart failure using the Tet-Off system. Eight weeks after the TAC operation, LV construction was preserved significantly by PPAR-α induction with an increase in PPAR-α-targeted genes related to fatty acid metabolism. The increase of expression of fibrosis-related genes was significantly attenuated by PPAR-α induction. Metabolic rates measured by isolated heart perfusions showed a reduction in FAO and glucose oxidation in TAC hearts, but the rate of FAO preserved significantly owing to the induction of PPAR-α. Myocardial high-energy phosphates were significantly preserved by PPAR-α induction. These results suggest that PPAR-α activation during pressure-overloaded heart failure improved myocardial function and energetics. Thus activating PPAR-α and modulation of FAO could be a promising therapeutic strategy for heart failure.
NEW & NOTEWORTHY The present study demonstrates the role of PPAR-α activation in the early stage of heart failure using an inducible transgenic mouse model. Induction of PPAR-α preserved heart function, and myocardial energetics. Activating PPAR-α and modulation of fatty acid oxidation could be a promising therapeutic strategy for heart failure.

Source: AJP: Heart and Circulatory Physiology - February 16, 2017 Category: Cardiology Authors: Kaimoto, S., Hoshino, A., Ariyoshi, M., Okawa, Y., Tateishi, S., Ono, K., Uchihashi, M., Fukai, K., Iwai-Kanai, E., Matoba, S. Tags: RESEARCH ARTICLE Source Type: research