Analyzing animal model morphometrics and the cardiac proteome in heart failure with preserved ejection fraction

Abstract

Introduction and Aims: Heart failure with preserved ejection fraction (HFpEF) is a diastolic dysfunction with unknown underlying mechanisms and etiology. A HFpEF mouse model was recently established, with mice on a high fat diet and water containing L-NAME which induces hypertension. A double knockout (dKO) of Obscurin/Obscurin-like1 (Obsl1) may also serve as a new model for HFpEF. The main purpose of this study is to investigate and compare changes to cardiac proteome between healthy lean mice, HFpEF mice and obscurin/Obsl1 dKO mice. Methods: Cardiac samples from three male and three female HFpEF mice (HFL) were compared with three male and three female healthy lean mice (SFD). Depletion of actomyosin was made using dilution buffer and centrifugation, and before the samples were sent off to mass spectrometry for proteome-analysis, they were analyzed using SDS-page gel to see if the depletion had worked. Pre-existing lung-sections were deparaffinized and stained with Prussian Blue, pictures were then taken, and the HFC were counted. Student´s T-test and ANOVA with Post-Hoc Tukey test was used for statistical analysis between the groups on the proteomes, heart failure cells (HFC) and pre-existing data of the body weight, tibia lengths, water content in lungs and kidneys Results: 128 significantly changed proteins found in the females, 56 in the males. HFL mice express significantly higher mean water content in lungs and kidneys. The HFL and dKO mice are significantly heavier than the SFD. No difference in tibia lengths. Significantly greater amount of HFC in dKO mice. Conclusions: The results support the idea of HFpEF being a sex-specific disease that affects females more than males. Most proteins that are found in both the HFL and Obscurin/Obsl1 models are involved in the cardiac metabolism, mitochondrial function or in cardiac contractility, which supports the idea of the dKO model being a future HFpEF model.