title: A high-lipid diet potentiates left ventricular dysfunction in nitric oxide synthase 3-deficient mice after chronic pressure overload.
abstract: A high-lipid diet (HLD) may lead to adverse left ventricular (LV) remodeling and endothelial dysfunction in conditions of hemodynamic stress. Although congenital absence of nitric oxide synthase 3 (NOS3) leads to adverse LV remodeling after transverse aortic constriction (TAC), the effects of a HLD in this state remains unknown. Wild-type (WT) and NOS3 knockout mice (NOS3(-/-)) were randomized into the following 4 groups: 1) WT + low-lipid diet (LLD) (10% of energy); 2) WT + HLD (60% of energy); 3) NOS3(-/-) + LLD; and 4) NOS3(-/-) + HLD for a total of 12 wk. After 1 wk of randomization, TAC was performed on all groups. Serial echocardiography revealed a decrease in LV ejection fraction (LVEF) in WT and NOS3(-/-) mice fed the HLD compared with those fed the LLD diet at 12 wk post-TAC. Mice fed the NOS3(-/-) + HLD diet had a lower LVEF compared with mice in the other 3 groups (P < 0.05). There was greater myocyte hypertrophy, interstitial fibrosis, and percentage change in plasma cholesterol concentrations in the NOS3(-/-) + HLD group 12 wk post-TAC compared with the other 3 groups. Although high molecular weight fibroblast growth factor-2, a marker of cardiac hypertrophy, was more upregulated in the NOS3(-/-) + HLD group than in the other groups, markers of the renin-angiotensin system did not differ among them. A HLD potentiates LV dysfunction in NOS3(-/-) mice in a chronic pressure overload state.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Roien
authors.initials: R
authors.lastname: Ahmadie
authors.forename: Jon-Jon
authors.initials: JJ
authors.lastname: Santiago
authors.forename: Jonathan
authors.initials: J
authors.lastname: Walker
authors.forename: Tielan
authors.initials: T
authors.lastname: Fang
authors.forename: Khuong
authors.initials: K
authors.lastname: Le
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhao
authors.forename: Nazila
authors.initials: N
authors.lastname: Azordegan
authors.forename: Sheri
authors.initials: S
authors.lastname: Bage
authors.forename: Matthew
authors.initials: M
authors.lastname: Lytwyn
authors.forename: Sunil
authors.initials: S
authors.lastname: Rattan
authors.forename: Ian M C
authors.initials: IM
authors.lastname: Dixon
authors.forename: Elissavet
authors.initials: E
authors.lastname: Kardami
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Moghadasian
authors.forename: Davinder S
authors.initials: DS
authors.lastname: Jassal
mesh_terms: D000818:Animals; D001011:Aorta; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003250:Constriction; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects*; D004452:Echocardiography; D002149:Energy Intake; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006352:Heart Ventricles / Q000473:pathology; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008970:Molecular Weight; D032342:Muscle Cells / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D004041:Dietary Fats; D016222:Fibroblast Growth Factor 2; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse