Journal article

Publication year: 2013

Pages: 1205-1218

Journal: The American Journal of Pathology

Volume number: 182

Issue number: 4

ISSN: 0002-9440

Open access status: Bronze

DOI Link: https://doi.org/10.1016/j.ajpath.2012.12.027

Publisher: Elsevier

Abstract: 
Despite recent advances in understanding the relevance of cell adhesion related signaling in the pathogenesis of ischemic cardiomyopathy (ICM) in animal models, substantial questions remain unanswered in the human setting. We have previously shown that the neural cell adhesion molecule CD56 [neural cell adhesion molecule (NCAM1)] is specifically overexpressed in ICM; it was the aim of the current study to further elucidate the role of CD56 in the pathogenesis of human ICM. We used quantitative real-time PCR and IHC in human ICM and a rat model of coronary obstruction to demonstrate that CD56(140kD), the only extraneuronally expressed NCAM1 isoform with a cytoplasmic protein domain capable of inducing intracellular signaling, is the only up-regulated CD56 isoform in failing cardiomyocytes in human ICM in vivo. In subsequent analyses of the cellular effects of CD56(140kD) overexpression in the development of ICM using differential whole transcriptome expression analyses and functional in vitro cardiomyocyte cell culture assays, we further show that the up-regulation of CD56(140kD) is associated with profound gene expression changes, increased apoptosis, and reduced Ca2+ signaling in failing human cardiomyocytes. Because apoptosis and Ca2+-related sarcomeric dysfunction are molecular hallmarks of ICM in humans, our results provide strong evidence that CD56(140kD) up-regulation plays a pivotal role in the pathogenesis of ICM and may be a target for future immunotherapeutic strategies in the treatment of this common and often fatal disease.

Harvard Citation style: Tur, M., Etschmann, B., Benz, A., Leich, E., Waller, C., Schuh, K., et al. (2013) The 140-kD Isoform of CD56 (NCAM1) Directs the Molecular Pathogenesis of Ischemic Cardiomyopathy, The American Journal of Pathology, 182(4), pp. 1205-1218. https://doi.org/10.1016/j.ajpath.2012.12.027

APA Citation style: Tur, M., Etschmann, B., Benz, A., Leich, E., Waller, C., Schuh, K., Rosenwald, A., Ertl, G., Kienitz, A., Haaf, A., Braeuninger, A., & Gattenloehner, S. (2013). The 140-kD Isoform of CD56 (NCAM1) Directs the Molecular Pathogenesis of Ischemic Cardiomyopathy. The American Journal of Pathology. 182(4), 1205-1218. https://doi.org/10.1016/j.ajpath.2012.12.027