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Cyclophilin A in Arrhythmogenic Cardiomyopathy Cardiac Remodeling

Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino IRCCS, 20138 Milano, Italy
Cardiac Arrhythmia Research Centre, Centro Cardiologico Monzino IRCCS, 20138 Milano, Italy
Treviso Tissue Bank Foundation, 31100 Treviso, Italy
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, 20126 Milano, Italy
Department of Cardiovascular Surgery, Centro Cardiologico Monzino IRCCS, 20138 Milano, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Int. J. Mol. Sci. 2019, 20(10), 2403;
Received: 15 April 2019 / Revised: 7 May 2019 / Accepted: 12 May 2019 / Published: 15 May 2019
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration)
PDF [4676 KB, uploaded 15 May 2019]


Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder characterized by the progressive substitution of functional myocardium with noncontractile fibro-fatty tissue contributing to ventricular arrhythmias and sudden cardiac death. Cyclophilin A (CyPA) is a ubiquitous protein involved in several pathological mechanisms, which also characterize ACM (i.e., fibrosis, inflammation, and adipogenesis). Nevertheless, the involvement of CyPA in ACM cardiac remodeling has not been investigated yet. Thus, we first evaluated CyPA expression levels in the right ventricle (RV) tissue specimens obtained from ACM patients and healthy controls (HC) by immunohistochemistry. Then, we took advantage of ACM- and HC-derived cardiac mesenchymal stromal cells (C-MSC) to assess CyPA modulation during adipogenic differentiation. Interestingly, CyPA was more expressed in the RV sections obtained from ACM vs. HC subjects and positively correlated with the adipose replacement extent. Moreover, CyPA was upregulated at early stages of C-MSC adipogenic differentiation and was secreted at higher level over time in ACM- derived C-MSC. Our study provides novel ex vivo and in vitro information on CyPA expression in ACM remodeling paving the way for future C-MSC-based mechanistic and therapeutic investigations. View Full-Text
Keywords: cyclophilin A; arrhythmogenic cardiomyopathy; cardiac mesenchymal stromal cells; adipogenesis; fibrosis cyclophilin A; arrhythmogenic cardiomyopathy; cardiac mesenchymal stromal cells; adipogenesis; fibrosis

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Rurali, E.; Pilato, C.A.; Perrucci, G.L.; Scopece, A.; Stadiotti, I.; Moschetta, D.; Casella, M.; Cogliati, E.; Sommariva, E.; Pompilio, G.; Nigro, P. Cyclophilin A in Arrhythmogenic Cardiomyopathy Cardiac Remodeling. Int. J. Mol. Sci. 2019, 20, 2403.

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