ABSTRACT
[Figure: see text].
Subject(s)
Coronary Artery Disease/genetics , Genetic Variation , Scavenger Receptors, Class B/genetics , Adult , Age of Onset , Animals , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Female , Genetic Association Studies , Genetic Predisposition to Disease , HEK293 Cells , Hep G2 Cells , Hepatocytes/metabolism , Heredity , Heterozygote , Humans , Induced Pluripotent Stem Cells/metabolism , Male , Mice, Inbred C57BL , Middle Aged , Pedigree , Phenotype , Risk Assessment , Risk Factors , Scavenger Receptors, Class B/metabolism , Severity of Illness Index , Exome SequencingABSTRACT
Ankyrin-B (encoded by ANK2), originally identified as a key cytoskeletal-associated protein in the brain, is highly expressed in the heart and plays critical roles in cardiac physiology and cell biology. In the heart, ankyrin-B plays key roles in the targeting and localization of key ion channels and transporters, structural proteins, and signaling molecules. The role of ankyrin-B in normal cardiac function is illustrated in animal models lacking ankyrin-B expression, which display significant electrical and structural phenotypes and life-threatening arrhythmias. Further, ankyrin-B dysfunction has been associated with cardiac phenotypes in humans (now referred to as "ankyrin-B syndrome") including sinus node dysfunction, heart rate variability, atrial fibrillation, conduction block, arrhythmogenic cardiomyopathy, structural remodeling, and sudden cardiac death. Here, we review the diverse roles of ankyrin-B in the vertebrate heart with a significant focus on ankyrin-B-linked cell- and molecular-pathways and disease.
