title: Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Groupe de Recherche en Valvulopathies, Centre de Recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Canada.
authors.forename: Wahiba
authors.initials: W
authors.lastname: Dhahri
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
authors.forename: Élise
authors.initials: É
authors.lastname: Roussel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
mesh_terms: D000818:Animals; D001022:Aortic Valve Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D025221:Phosphofructokinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D025221:Phosphofructokinases; D011345:Fenofibrate