Characterization of Fibrosis and Hypertrophy in a Feline Model of HFpEF

Abstract

Rationale: Heart failure with preserved ejection fraction (HFpEF) is rapidly growing as a major public health problem and there are no proven therapeutics available. This lack of therapeutics may be partially attributed to the lack of well-established animal models and understanding of the underlying pathophysiology. Aim: Our aim was to complete an in-depth fibrotic and hypertrophy analysis of the feline HFpEF heart. Methods and Results: Male kittens, age 2 months, underwent aortic banding to induce a slow, progressive pressure overload resulting in a HFpEF phenotype. Four months after banding, terminal studies were conducted after which the heart was explanted and underwent a histological work up. The fibrotic area was examined using Masson’s trichrome staining and cardiomyocyte cross-sectional area was examined by staining for the cell membrane. There was a significant increase in left ventricle fibrosis in banded cats compared to sham animals. In banded cats, the sub-endocardial layer of the left ventricle had more fibrosis than the sub-epicardial layer of the left ventricle. There was an increase in fibrosis in the left atrium, right atrium, and right ventricle in the banded animals compared to the sham animals, but it did not reach statistical significance. There was a significant increase in the cardiomyocyte cross-sectional area of banded cats compared to sham cats. Conclusions: An in-depth analysis of the feline HFpEF heart revealed important insights into the state of fibrosis and hypertrophy, which further supports the use of this model as pre-clinical platform for testing therapeutics.