Abstract P2022: Ankyrin-R Isoforms Are Differentially Expressed in Cardiac Tissues under Stress

Heart disease remains the leading cause of death in the United States with heart failure specifically accounting for 13.4% of all heart disease related deaths. In 2019, Andersson et al., utilized a multi-omics approach to evaluate participant samples from the Framingham Heart Study and showed that ankyrin-R (AnkR; encoded by ANK1 ) is significantly associated with diastolic function, left ventricular remodeling and heart failure with preserved ejection fraction. Ankyrins are a family of proteins that link integral membrane proteins with the actin/β-spectrin cytoskeleton. Ankyrins-B/G have been extensively studied and identified within the heart and their dysfunction is associated with cardiac structural and electrical phenotypes. Ankyrin-R was first identified in red blood cells and has yet to be studied in the context of cardiac function and heart failure or arrhythmia disease. To study AnkR in the context of the heart we isolated perfused tissues from adult wild-type mice and performed immunoblot and qPCR analysis on ankyrin-R protein and Ank1 mRNA expression. The large AnkR isoform is expressed in the heart, along with the brain, intestine, and spleen. Interestingly, only the heart showed expression of a small AnkR isoform that has previously been shown to interact with the sarcoplasmic protein obscurin. Notably, isolated cardiomyocytes express the small AnkR isoform while cardiac fibroblasts express the canonical large AnkR isoform at both the protein and mRNA level. Canonical AnkR is diffusely expressed in the fibroblast membrane, cytoplasm, cytoskeleton, and soluble nuclear fractions. Interestingly, this expression pattern is switched under stressed conditions where cardiomyocytes increase and cardiac fibroblasts decrease their canonical AnkR expression, respectively. These preliminary results are the first to show canonical AnkR expression in the mouse myocardium specifically within the cardiac fibroblasts and allude that AnkR’s utilization during cardiac stress is cell-type dependent. Future studies will seek to define molecular, cell, and organ phenotypes related to AnkR in the heart.