AIMS: Fenofibrate is a peroxisome proliferator-associated receptor alpha agonist (PPARα) used clinically for the management of dyslipidemia and is a myocardial fatty acid oxidation stimulator. It has also been shown to have cardiac anti-hypertrophic properties but the effects of fenofibrate on the development of eccentric LVH and ventricular function in chronic left ventricular (LV) volume overload (VO) are unknown. This study was therefore designed to explore the effects of fenofibrate treatment in a VO rat model caused by severe aortic valve regurgitation (AR) with a focus on cardiac remodeling and myocardial metabolism. MAIN METHODS: Male Wistar rats were divided in four groups (13-15 animals/group): Shams (S) treated with fenofibrate (F; 100 mg/kg/d PO) or not (C) and severe AR receiving or not fenofibrate. Treatment was started one week before surgery and the animals were sacrificed 9 weeks later. KEY FINDINGS: AR rats developed severe LVH (increased LV weight) during the course of the protocol. Fenofibrate did not reduce LV weight. However, eccentric LV remodeling was strongly reduced by fenofibrate in AR animals. Fractional shortening was significantly less affected in ARF compared to ARC group. Fenofibrate also increased the myocardial enzymatic activity of enzymes associated with fatty acid oxidation while inhibiting glycolytic enzyme phosphofructokinase. SIGNIFICANCE: Fenofibrate decreased LV eccentric remodeling associated with severe VO and helped maintain systolic function. Studies with a longer follow-up will be needed to assess the long-term effects of fenofibrate in chronic volume overload caused by aortic regurgitation.
AIMS: Fenofibrate is a peroxisome proliferator-associated receptor alpha agonist (PPARα) used clinically for the management of dyslipidemia and is a myocardial fatty acid oxidation stimulator. It has also been shown to have cardiac anti-hypertrophic properties but the effects of fenofibrate on the development of eccentric LVH and ventricular function in chronic left ventricular (LV) volume overload (VO) are unknown. This study was therefore designed to explore the effects of fenofibrate treatment in a VO rat model caused by severe aortic valve regurgitation (AR) with a focus on cardiac remodeling and myocardial metabolism. MAIN METHODS: Male Wistar rats were divided in four groups (13-15 animals/group): Shams (S) treated with fenofibrate (F; 100 mg/kg/d PO) or not (C) and severe AR receiving or not fenofibrate. Treatment was started one week before surgery and the animals were sacrificed 9 weeks later. KEY FINDINGS: AR rats developed severe LVH (increased LV weight) during the course of the protocol. Fenofibrate did not reduce LV weight. However, eccentric LV remodeling was strongly reduced by fenofibrate in AR animals. Fractional shortening was significantly less affected in ARF compared to ARC group. Fenofibrate also increased the myocardial enzymatic activity of enzymes associated with fatty acid oxidation while inhibiting glycolytic enzyme phosphofructokinase. SIGNIFICANCE: Fenofibrate decreased LV eccentric remodeling associated with severe VO and helped maintain systolic function. Studies with a longer follow-up will be needed to assess the long-term effects of fenofibrate in chronic volume overload caused by aortic regurgitation.
Authors: Saranya Ravi; Traci L Parry; Monte S Willis; Pamela Lockyer; Cam Patterson; James R Bain; Robert D Stevens; Olga R Ilkayeva; Christopher B Newgard; Jonathan C Schisler Journal: J Cardiovasc Dev Dis Date: 2018-08-15
Authors: Elise Roussel; Marie-Claude Drolet; Elisabeth Walsh-Wilkinson; Wahiba Dhahri; Dominic Lachance; Suzanne Gascon; Otman Sarrhini; Jacques A Rousseau; Roger Lecomte; Jacques Couet; Marie Arsenault Journal: Biomed Res Int Date: 2015-10-25 Impact factor: 3.411