Nucleoporins in cardiovascular disease

Abstract

Cardiovascular disease is a pressing health problem with significant global health, societal, and financial burdens. Understanding the molecular basis of polygenic cardiac pathology is thus essential to devising novel approaches for management and treatment. Recent identification of uncharacterized regulatory functions for a class of nuclear envelope proteins called nucleoporins offers the opportunity to understand novel putative mechanisms of cardiac disease development and progression. Consistent reports of nucleoporin deregulation associated with ischemic and dilated cardiomyopathies, arrhythmias and valvular disorders suggests that nucleoporin impairment may be a significant but understudied variable in cardiopathologic disorders. This review discusses and converges existing literature regarding nuclear pore complex proteins and their association with cardiac pathologies, and proposes a role for nucleoporins as facilitators of cardiac disease.

Keywords: arrhythmia; cardiomyopathy; cardiopathologies; nuclear pore complex; nucleoporin.

Figure 1.

Schematic illustration of the Nuclear Pore Complex (NPC) depicting the location of known nucleoporins, and their subcomplexes, within the NPC. Highlighted (*) are the mobile nucleoporins. CCR = central channel region, IR = inner ring, NB = nuclear basket, OR = outer rings.

Figure 2.

Nucleoporins associated with cardiac disorders. Representative illustration of nucleoporins associated with cardiac disorders and their localization within the nuclear pore complex, with each group highlighted in different colors. Nucleoporins associated with dilated and ischemic cardiomyopathy are highlighted in pink (NUP358, NUP62, NDC1, NUP93, NUP160, NUP153), valve disorders in blue (NUP43, NUP188), congestive heart failure (HF) in green (NUP85), heterotaxy and situs inversus in purple (NUP188, NUP205, NUP210) and arrhythmias in orange (NUP155, NUP107, NUP37, NUP153)