CELF1 Mediates Connexin 43 mRNA Degradation in Dilated Cardiomyopathy

Abstract

Our results suggest a mechanism for increased CELF1 expression downregulating Cx43 mRNA level and a pathogenic role for elevated CELF1 level in the DCM heart.

CELF1 regulates gap junction integrity contributing to dilated cardiomyopathy

“…Additionally, cardiovascular disease has become a significant economic strain to the health care system with continuous hospitalization (4) as well as high morbidity and mortality (5). Cardiovascular disease can be caused by a variety of different factors including cell-to-cell communication defects that result in a breakdown between important cell connections (6). A malfunction of cell-to-cell communication in the myocardium can lead to pathologic cardiac remodeling which can ultimately result in heart disease (6).…”

“…Cardiovascular disease can be caused by a variety of different factors including cell-to-cell communication defects that result in a breakdown between important cell connections (6). A malfunction of cell-to-cell communication in the myocardium can lead to pathologic cardiac remodeling which can ultimately result in heart disease (6). …”

“…Cell-to-cell communication is important for healthy heart function, and importantly, disruptions to this necessary coupling event can lead to ventricular arrhythmias (6,7,9,13). This connection processes occur through intercalated discs within the cardiac muscle, and consist of three complexes including gap junctions, fascia adherins, and desmosomes (7).…”

“…Gap junctions are cell passages that help exchange micro-molecular metabolites to coordinate electrical activity (10,13). They rely on connexin isoforms in order to carry out cardiac conduction (6–8,14,15). Each individual gap junction is composed of two hemichannels or connexons (13,14).…”

“…Cx43 is typically located at intercalated discs of cardiomyocytes (13) and is predominantly expressed between the ventricular and atrial myocytes (5). Impulse conduction changes can result from an anomalous expression of important gap junction proteins such as Cx43 (6,13–15) which can lead to arrhythmias, DCM, and ultimately heart failure (5,6,13). DCM patients for example, display significantly decreased Cx43 expression levels (6–9), while it is thought that an increase in Cx43 expression is a part of the adaptive cardiac pathologic remodeling phase (6).…”