Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls.

Akdis, Deniz; Medeiros Domingo, Argelia; Gaertner-Rommel, Anna; Kast, Jeannette I; Enseleit, Frank; Bode, Peter; Klingel, Karin; Kandolf, Reinhard; Renois, Fanny; Andreoletti, Laurent; Akdis, Cezmi A; Milting, Hendrik; Lüscher, Thomas F; Brunckhorst, Corinna; Saguner, Ardan M; Duru, Firat (2016). Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls. Heart rhythm, 13(3), pp. 731-741. Elsevier 10.1016/j.hrthm.2015.11.010

[img] Text
1-s2.0-S154752711501396X-main.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is mainly an autosomal dominant disease characterized by fibrofatty infiltration of the right ventricle, leading to ventricular arrhythmias. Mutations in desmosomal proteins can be identified in about half of the patients. The pathogenic mechanisms leading to disease expression remain unclear. OBJECTIVE The purpose of this study was to investigate myocardial expression profiles of candidate molecules involved in the pathogenesis of ARVC/D. METHODS Myocardial messenger RNA (mRNA) expression of 62 junctional molecules, 5 cardiac ion channel molecules, 8 structural molecules, 4 apoptotic molecules, and 6 adipogenic molecules was studied. The averaged expression of candidate mRNAs was compared between ARVC/D samples (n = 10), nonfamilial dilated cardiomyopathy (DCM) samples (n = 10), and healthy control samples (n = 8). Immunohistochemistry and quantitative protein expression analysis were performed. Genetic analysis using next generation sequencing was performed in all patients with ARVC/D. RESULTS Following mRNA levels were significantly increased in patients with ARVC/D compared to those with DCM and healthy controls: phospholamban (P ≤ .001 vs DCM; P ≤ .001 vs controls), healthy tumor protein 53 apoptosis effector (P = .001 vs DCM; P ≤ .001 vs controls), and carnitine palmitoyltransferase 1β (P ≤ .001 vs DCM; P = 0.008 vs controls). Plakophillin-2 (PKP-2) mRNA was downregulated in patients with ARVC/D with PKP-2 mutations compared with patients with ARVC/D without PKP-2 mutations (P = .04). Immunohistochemistry revealed significantly increased protein expression of phospholamban, tumor protein 53 apoptosis effector, and carnitine palmitoyltransferase 1β in patients with ARVC/D and decreased PKP-2 expression in patients with ARVC/D carrying a PKP-2 mutation. CONCLUSION Changes in the expression profiles of sarcolemmal calcium channel regulation, apoptosis, and adipogenesis suggest that these molecular pathways may play a critical role in the pathogenesis of ARVC/D, independent of the underlying genetic mutations.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Medeiros Domingo, Argelia

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1547-5271

Publisher:

Elsevier

Language:

English

Submitter:

Argelia Medeiros Domingo

Date Deposited:

04 Mar 2016 07:13

Last Modified:

06 Mar 2016 08:09

Publisher DOI:

10.1016/j.hrthm.2015.11.010

PubMed ID:

26569459

Uncontrolled Keywords:

Adipogenesis; Apptosis; Arrhythmogenic right ventricular; Cardiomyopathy; Dysplasia; Phospholamban

BORIS DOI:

10.7892/boris.76263

URI:

https://boris.unibe.ch/id/eprint/76263

Actions (login required)

Edit item Edit item
Provide Feedback