학술논문
Heart failure after pressure overload in autosomal-dominant desminopathies: Lessons from heterozygous DES-p.R349P knock-in mice
Document Type
Academic Journal
Author
Stöckigt, Florian; Eichhorn, Lars; Beiert, Thomas; Knappe, Vincent; Radecke, Tobias; Steinmetz, Martin; Nickenig, Georg; Peeva, Viktoriya; Kudin, Alexei P.; Kunz, Wolfram S.; Berwanger, Carolin; Kamm, Lisa; Schultheis, Dorothea; Schlötzer-Schrehardt, Ursula; Clemen, Christoph S.; Schröder, Rolf; Schrickel, Jan W.
Source
PLoS ONE. March 3, 2020, Vol. 15 Issue 3, e0228913
Subject
Language
English
ISSN
1932-6203
Abstract
Background Mutations in the human desmin gene (DES) cause autosomal-dominant and -recessive cardiomyopathies, leading to heart failure, arrhythmias, and AV blocks. We analyzed the effects of vascular pressure overload in a patient-mimicking p.R349P desmin knock-in mouse model that harbors the orthologue of the frequent human DES missense mutation p.R350P. Methods and results Transverse aortic constriction (TAC) was performed on heterozygous (HET) DES-p.R349P mice and wild-type (WT) littermates. Echocardiography demonstrated reduced left ventricular ejection fraction in HET-TAC (WT-sham: 69.5 ± 2.9%, HET-sham: 64.5 ± 4.7%, WT-TAC: 63.5 ± 4.9%, HET-TAC: 55.7 ± 5.4%; p Conclusion Pressure overload in HET mice aggravated the clinical phenotype of cardiomyopathy and resulted in mitochondrial dysfunction. Preventive avoidance of pressure overload/arterial hypertension in desminopathy patients might represent a crucial therapeutic measure.
Author(s): Florian Stöckigt 1,2,*, Lars Eichhorn 3, Thomas Beiert 1, Vincent Knappe 1, Tobias Radecke 4, Martin Steinmetz 4, Georg Nickenig 1, Viktoriya Peeva 5,6, Alexei P. Kudin 5,6, Wolfram [...]
Author(s): Florian Stöckigt 1,2,*, Lars Eichhorn 3, Thomas Beiert 1, Vincent Knappe 1, Tobias Radecke 4, Martin Steinmetz 4, Georg Nickenig 1, Viktoriya Peeva 5,6, Alexei P. Kudin 5,6, Wolfram [...]