Investigating Cardiac Protein Expression in two Diastolic Heart Failure Mouse Models

Abstract

Introduction / Background: The treatment of heart failure with preserved ejection fraction (HFpEF) remains challenging as common heart failure drugs fail to reduce mortality in the patient group. There is a lack of knowledge of what molecular mechanisms are responsible for the disease and a lack of animal models to emulate the disease. There are however two new HFpEF mouse models, the High Fat diet + L-NAME (HFL) mouse model and the Obscurin/Obsl1 dKO model. Aim(s) / Objective(s): To investigate the expression profile of key structural, metabolic and sarcoplasmic reticulum (SR) proteins in the HFL mouse model and to compare the results with previous unpublished results from the Obscurin/Obsl1 mouse model. Methods: The concentration of 24 different proteins in 3 female and male controls as well as 3 female and male HFL mice were investigated using western blotting. The blots were then quantified using the computer program Fiji and analyzed using SPSS. The localization of Obscurin, Obsl1 and smooth muscle actin inside the tissue was visualized using immunofluorescence. Results: In female HFL mice, a statistically significant decrease of Obscurin and an increase of Obsl1 was seen. No change was seen in male mice. For metabolism, protein changes that indicate a metabolic switch to increased fat metabolism was seen. In the sarcoplasmic reticulum (SR) there were significant changes calcium handling proteins. Conclusion(s) / Implication(s): Both models saw changes to SR proteins, but the specific proteins affected differed between the models. However, there are signs that both SR function and the expression of structural proteins Obscurin and Obsl1 are affected in the disease and could be underlying mechanisms. The metabolic profile on the other hand does not seem to be altered in any specific way in the disease.