Abstract 19914: Female Sex Hormones Do not Protect Against Cardiomyocyte Dysfunction in Aortic-Banded Miniature-Swine
Introduction: Population studies have shown the prevalence of HFpEF sharply increases in women after menopause. Sex differences in cardiomyocyte function may play a role in the development of HFpEF. Thus, the purpose of this study was to determine the impact of ovariectomy (OVX) on cardiomyocyte function in a female mini-swine model of pressure-overload HF induced by aortic-banding (AB). We hypothesized female sex hormones would protect against AB-induced cardiomyocyte calcium handling abnormalities and contractile dysfunction.
Methods: Female mini-swine were divided into 4 groups; CON (n=6; 47 cells), OVX (n=6; 53 cells), AB (n=6; 51 cells) and AB-OVX (n=7; 51 cells). OVX and AB procedures occurred at 7 and 8 mo. of age, respectively. Six months post-AB, calcium handling and contractile function were measured outside the estrus phase in isolated left ventricular (LV) cardiomyocytes loaded with Fura-2 and stimulated at 0.5Hz. Protein levels (western blot) of the sarco-endoplasmic reticulum calcium-ATPase (SERCA), phospholamban (PLB), and phosphorylated PLB at the threonine-17 (Thr17) site were assessed. Significance was set at P < 0.05 using 2x2 ANOVA (OVX x AB) reported by main effect (ME) or interaction (INT).
Results: Pressure-overload increased LV diastolic wall thickness (ME of AB) without altering internal diastolic dimension (i.e. concentric hypertrophy). Both cardiomyocyte shortening amplitude (ME of AB; CON vs. AB, OVX vs. AB-OVX) and calcium transient amplitude (ME of AB; CON vs. AB) were decreased following pressure-overload. Aortic banding also impaired calcium reuptake (increased Tau - ME of AB; CON vs. AB). SERCA and PLB protein levels were increased in all groups vs. CON (INT). Pressure-overload decreased phosphorylation of PLB at Thr17 (ME of AB; CON vs. AB).
Conclusions: Contrary to our hypothesis, female sex hormones do not protect against pressure-overload induced cardiomyocyte dysfunction. Impaired cardiomyocyte shortening and calcium transients may be due to decreased sarcoplasmic reticulum calcium sequestration resulting from reduced phosphorylation of PLB at Thr17. Our results show impaired cardiomyocyte function contributes to pressure-overload HF in a translational model with potential relevance to human HFpEF.
Author Disclosures: J.A. Hiemstra: None. T.D. Olver: None. J.C. Edwards: None. M.D. Lambert: None. J.R. Ivey: None. P.K. Thorne: None. K.S. McDonald: None. T.L. Domeier: None. C.A. Emter: None.
- © 2016 by American Heart Association, Inc.