Induction of Nogo‐A in Cardiomyopathy

Abstract

The Nogo isoforms A, B, and C are part of a superfamily of proteins termed the reticulons, from the same gene (Nogo/RTN4), share a c‐terminal domain, and are thought to have preferential ER localization. Nogo‐A has been traditionally described as a myelin associated inhibitor of axonal sprouting, with a molecular weight of ~160 kilodaltons (kDa) limited tissue distribution, and multiple transmembrane domains. There is a vast amount of data examining the function of the Nogo reticulon protein family, particularly with respect to neuronal plasticity however, very little is known about the Nogo proteins in the heart. In failing human heart samples we saw a 3 fold increase in Nogo‐A, vs nonfailing by western immunoanalysis (n=5). RT‐PCR of isolated human cardiac fibroblasts showed a 3 fold increase in nogo‐A mRNA with 2 hours of cyclic stretch. Western analysis of PKC epsilon overexpressing heart extracts showed increased levels of Nogo‐A, corresponding to the development of the dilated phenotype. Isolated cardiomyocyte experiment demonstrate an increase in Nogo‐A with mechanical stretch but not with hypertrophic agonist treatment. We propose an increase Nogo‐A in the heart is an adaptive mechanoresponse.