Dataset Information

Arrythmogenic right ventricular acrdiomayopathy (PKP2-cko in mice and Human biopsies)

ABSTRACT: Summary: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder. It is classified as the second most common cause of unexpected sudden death by cardiac arrest in the young. ARVC has devastating psychosocial consequences, especially as many patients are young adults, and current therapy is limited to extreme exercise restriction and defibrillator implantation. More than 40% of the reported genetic variants linked to ARVC reside in a gene called PKP2 , which encodes for the plakophilin-2 (PKP2) protein. The pathogenic mechanisms linking this protein to ARVC remain to be elucidated, which is the focus of this project. I aim to identify exactly which proteins in the heart are dysregulated and to identify why exercise is detrimental for carriers of PKP2-deficient hearts. Our approach is based on state-of-the-art mass spectrometry (MS) technologies that allow us to measure all proteins in the heart simultaneously. We used both human heart biopsy material as well as a murine disease model I anticipate to elucidate novel roles of PKP2 that are of utmost importance for understanding ARVC pathogenesis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Heart

DISEASE(S): Arrhythmogenic Right Ventricular Cardiomyopathy

SUBMITTER: Navratan Bagwan

LAB HEAD: Alicia Lundby

PROVIDER: PXD025523 | Pride | 2022-11-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20200501_EXPL1_nLC14_LD_QC_MNT_ARCV_fr01.raw	Raw
	20200501_EXPL1_nLC14_LD_QC_MNT_ARCV_fr02.raw	Raw
	20200501_EXPL1_nLC14_LD_QC_MNT_ARCV_fr03.raw	Raw
	20200501_EXPL1_nLC14_LD_QC_MNT_ARCV_fr04.raw	Raw
	20200501_EXPL1_nLC14_LD_QC_MNT_ARCV_fr05.raw	Raw

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Publications

Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.

Pérez-Hernández Marta M van Opbergen Chantal J M CJM Bagwan Navratan N Vissing Christoffer Rasmus CR Marrón-Liñares Grecia M GM Zhang Mingliang M Torres Vega Estefania E Sorrentino Andrea A Drici Lylia L Sulek Karolina K Zhai Ruxu R Hansen Finn B FB Christensen Alex H AH Boesgaard Søren S Gustafsson Finn F Rossing Kasper K Small Eric M EM Davies Michael J MJ Rothenberg Eli E Sato Priscila Y PY Cerrone Marina M Jensen Thomas Hartvig Lindkær THL Qvortrup Klaus K Bundgaard Henning H Delmar Mario M Lundby Alicia A

Circulation 20220812 11

<h4>Background</h4>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the <i>PKP2</i> gene, which encodes the PKP2 protein (plakophilin-2).<h4>Methods</h4>We describe a comprehensive characterization of the ARVC molecular landscape as determined by high-resolution mass spectrometry, RNA sequencing, and transmission elect ...[more]

PMID: 35959657

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