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RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy.

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RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy.

dc.contributor.author	Hall, Charlotte L.
dc.contributor.author	Gurha, Priyatansh
dc.contributor.author	Sabater-Molina, Maria
dc.contributor.author	Asimaki, Angeliki
dc.contributor.author	Futema, Marta
dc.contributor.author	Lovering, Ruth C.
dc.contributor.author	Suárez, Mari Paz
dc.contributor.author	Aguilera, Beatriz
dc.contributor.author	Molina Aguilar, Pilar
dc.contributor.author	Zorio Grima, Esther
dc.contributor.author	Coarfa, Cristian
dc.contributor.author	Robertson, Matthew J.
dc.contributor.author	Cheedipudi, Sirisha M.
dc.contributor.author	Keat-Eng Ng.
dc.contributor.author	Delaney, Paul
dc.contributor.author	Hernández, Juan Pedro
dc.contributor.author	Pastor, Francisco
dc.contributor.author	Gimeno, Juan R.
dc.contributor.author	McKenna, William J.
dc.contributor.author	Marian, Ali J.
dc.contributor.author	Syrris, Petros
dc.date.accessioned	2021-04-19T06:51:56Z
dc.date.available	2021-04-19T06:51:56Z
dc.date.issued	2020
dc.identifier.citation	Hall, Charlotte L. Gurha, Priyatansh Sabater-Molina, Maria Asimaki, Angeliki Futema, Marta Lovering, Ruth C. Suárez, Mari Paz Aguilera, Beatriz Molina Aguilar, Pilar Zorio Grima, Esther Coarfa, Cristian Robertson, Matthew J. Cheedipudi, Sirisha M. Keat-Eng Ng. Delaney, Paul Hernández, Juan Pedro Pastor, Francisco Gimeno, Juan R. McKenna, William J. Marian, Ali J. Syrris, Petros 2020 RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy. International Journal of Cardiology 302 124 130
dc.identifier.uri	https://hdl.handle.net/10550/78744
dc.description.abstract	Arrhythmogenic cardiomyopathy (ACM) encompasses a group of inherited cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC) whose molecular disease mechanism is associated with dysregulation of the canonical WNT signalling pathway. Recent evidence indicates that ARVC and ACM caused by pathogenic variants in the FLNC gene encoding filamin C, a major cardiac structural protein, may have different molecular mechanisms of pathogenesis. We sought to identify dysregulated biological pathways in FLNC-associated ACM. RNA was extracted from seven paraffin-embedded left ventricular tissue samples from deceased ACM patients carrying FLNC variants and sequenced. Transcript levels of 623 genes were upregulated and 486 genes were reduced in ACM in comparison to control samples. The cell adhesion pathway and ILK signalling were among the prominent dysregulated pathways in ACM. Consistent with these findings, transcript levels of cell adhesion genes JAM2, NEO1, VCAM1 and PTPRC were upregulated in ACM samples. Moreover, several actin-associated genes, including FLNC, VCL, PARVB and MYL7, were suppressed, suggesting dysregulation of the actin cytoskeleton. Analysis of the transcriptome for biological pathways predicted activation of inflammation and apoptosis and suppression of oxidative phosphorylation and MTORC1 signalling in ACM. Our data suggests dysregulated cell adhesion and ILK signalling as novel putative pathogenic mechanisms of ACM caused by FLNC variants which are distinct from the postulated disease mechanism of classic ARVC caused by desmosomal gene mutations. This knowledge could help in the design of future gene therapy strategies which would target specific components of these pathways and potentially lead to novel treatments for ACM.
dc.language.iso	eng
dc.relation.ispartof	International Journal of Cardiology, 2020, vol. 302, p. 124-130
dc.subject	Patologia
dc.title	RNA sequencing-based transcriptome profiling of cardiac tissue Implicados novela putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy.
dc.type	journal article	es_ES
dc.date.updated	2021-04-19T06:51:57Z
dc.identifier.doi	10.1016/j.ijcard.2019.12.002
dc.identifier.idgrec	145248
dc.rights.accessRights	open access	es_ES