Modulation of cytoskeleton in cardiomyopathy caused by mutation in LMNA gene.

Abstract

Dilated cardiomyopathy caused by mutations in LMNA, encoding A-type lamins (i.e., LMNA cardiomyopathy), is characterized by a left ventricle enlargement and ultimately results in poor cardiac contractility associated with conduction disease. Despite current strategies to aggressively manage the symptoms, the disorder remains a common cause of sudden death and heart failure with decreased ejection fraction. Patients care includes cardioverter defibrillator implantation but the last therapeutic option remains cardiac transplantation. A-type lamins are intermediate filaments and are the main components of the nuclear lamina, a meshwork underlying the inner nuclear membrane, which plays an essential role in both maintaining the nuclear structure and organizing the cytoskeletal structures within the cell. Cytoskeletal proteins function as scaffold to resist external mechanical stress. An increasing amount of evidence demonstrates that LMNA mutations can lead to disturbances in several structural and cytoskeletal components of the cell such as microtubules, actin cytoskeleton and intermediate filaments. Collectively, this review focuses on the significance of these cytoskeletal modulators and emphasizes their potential therapeutic role in LMNA cardiomyopathy.