title: Dietary fish oil is antihypertrophic but does not enhance postischemic myocardial function in female mice.
abstract: Clinically and experimentally, a case for omega-3 polyunsaturated fatty acid (PUFA) cardioprotection in females has not been clearly established. The goal of this study was to investigate whether dietary omega-3 PUFA supplementation could provide ischemic protection in female mice with an underlying genetic predisposition to cardiac hypertrophy. Mature female transgenic mice (TG) with cardiac-specific overexpression of angiotensinogen that develop normotensive cardiac hypertrophy and littermate wild-type (WT) mice were fed a fish oil-derived diet (FO) or PUFA-matched control diet (CTR) for 4 wk. Myocardial membrane lipids, ex vivo cardiac performance (intraventricular balloon) after global no-flow ischemia and reperfusion (15/30 min), and reperfusion arrhythmia incidence were assessed. FO diet suppressed cardiac growth by 5% and 10% in WT and TG, respectively (P < 0.001). The extent of mechanical recovery [rate-pressure product (RPP) = beats/min x mmHg] of FO-fed WT and TG hearts was similar (50 +/- 7% vs. 45 +/- 12%, 30 min reperfusion), and this was not significantly different from CTR-fed WT or TG. To evaluate whether systemic estrogen was masking a protective effect of the FO diet, the responses of ovariectomized (OVX) WT and TG mice to FO dietary intervention were assessed. The extent of mechanical recovery of FO-fed OVX WT and TG (RPP, 50 +/- 4% vs. 64 +/- 8%) was not enhanced compared with CTR-fed mice (RPP, 60 +/- 11% vs. 80 +/- 8%, P = 0.335). Dietary FO did not suppress the incidence of reperfusion arrhythmias in WT or TG hearts (ovary-intact mice or OVX). Our findings indicate a lack of cardioprotective effect of dietary FO in females, determined by assessment of mechanical and arrhythmic activity postischemia in a murine ex vivo heart model.
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Huggins
authors.forename: Claire L
authors.initials: CL
authors.lastname: Curl
authors.forename: Ruchi
authors.initials: R
authors.lastname: Patel
authors.forename: Peter L
authors.initials: PL
authors.lastname: McLennan
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Theiss
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005395:Fish Oils / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006984:Hypertrophy / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*
chemical_list: D004042:Dietary Fats, Unsaturated; D004967:Estrogens; D005395:Fish Oils; D000808:Angiotensinogen; D000804:Angiotensin II