MyJournals Home  

RSS FeedsIJMS, Vol. 20, Pages 4076: Plakophilin-2 Haploinsufficiency Causes Calcium Handling Deficits and Modulates the Cardiac Response Towards Stress (International Journal of Molecular Sciences)

 
 

21 august 2019 14:00:20

 
IJMS, Vol. 20, Pages 4076: Plakophilin-2 Haploinsufficiency Causes Calcium Handling Deficits and Modulates the Cardiac Response Towards Stress (International Journal of Molecular Sciences)
 




Human variants in plakophilin-2 (PKP2) associate with most cases of familial arrhythmogenic cardiomyopathy (ACM). Recent studies show that PKP2 not only maintains intercellular coupling, but also regulates transcription of genes involved in Ca2+ cycling and cardiac rhythm. ACM penetrance is low and it remains uncertain, which genetic and environmental modifiers are crucial for developing the cardiomyopathy. In this study, heterozygous PKP2 knock-out mice (PKP2-Hz) were used to investigate the influence of exercise, pressure overload, and inflammation on a PKP2-related disease progression. In PKP2-Hz mice, protein levels of Ca2+-handling proteins were reduced compared to wildtype (WT). PKP2-Hz hearts exposed to voluntary exercise training showed right ventricular lateral connexin43 expression, right ventricular conduction slowing, and a higher susceptibility towards arrhythmias. Pressure overload increased levels of fibrosis in PKP2-Hz hearts, without affecting the susceptibility towards arrhythmias. Experimental autoimmune myocarditis caused more severe subepicardial fibrosis, cell death, and inflammatory infiltrates in PKP2-Hz hearts than in WT. To conclude, PKP2 haploinsufficiency in the murine heart modulates the cardiac response to environmental modifiers via different mechanisms. Exercise upon PKP2 deficiency induces a pro-arrhythmic cardiac remodeling, likely based on impaired Ca2+ cycling and electrical conduction, versus structural remodeling. Pathophysiological stimuli mainly exaggerate the fibrotic and inflammatory response.


Del.icio.us Digg Facebook Google StumbleUpon Twitter
 
27 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 20, Pages 4075: Microtubules: A Key to Understand and Correct Neuronal Defects in CDKL5 Deficiency Disorder? (International Journal of Molecular Sciences)
IJMS, Vol. 20, Pages 4073: Castration Induces Down-Regulation of A-Type K+ Channel in Rat Vas Deferens Smooth Muscle (International Journal of Molecular Sciences)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Molecular Biology

Use these buttons to bookmark us:
Del.icio.us Digg Facebook Google StumbleUpon Twitter


Valid HTML 4.01 Transitional
Copyright © 2008 - 2019 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Travel Photos Nachrichten Indigonet Finances Leer Mandarijn