TY  - JOUR
A1  - John, Cathleen
A1  - Grune, Jana
A1  - Ott, Christiane
A1  - Nowotny, Kerstin
A1  - Deubel, Stefanie
A1  - Kühne, Arne
A1  - Schubert, Carola
A1  - Kintscher, Ulrich
A1  - Regitz-Zagrosek, Vera
A1  - Grune, Tilman
T1  - Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse
JF  - Frontiers in Endocrinology
N2  - Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.
KW  - NZO
KW  - heart
KW  - obesity
KW  - mitochondrial function
KW  - echocardiography
KW  - systolic function
Y1  - 2018
U6  - https://doi.org/10.3389/fendo.2018.00732
SN  - 1664-2392
VL  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Nordmeyer, Sarah
A1  - Kraus, Milena
A1  - Ziehm, Matthias
A1  - Kirchner, Marieluise
A1  - Schafstedde, Marie
A1  - Kelm, Marcus
A1  - Niquet, Sylvia
A1  - Stephen, Mariet Mathew
A1  - Baczko, Istvan
A1  - Knosalla, Christoph
A1  - Schapranow, Matthieu-Patrick
A1  - Dittmar, Gunnar
A1  - Gotthardt, Michael
A1  - Falcke, Martin
A1  - Regitz-Zagrosek, Vera
A1  - Kuehne, Titus
A1  - Mertins, Philipp
T1  - Disease- and sex-specific differences in patients with heart valve disease
BT  - a proteome study
JF  - Life Science Alliance
N2  - Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease-and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies.
Y1  - 2023
U6  - https://doi.org/10.26508/lsa.202201411
SN  - 2575-1077
VL  - 6
IS  - 3
PB  - EMBO Press
CY  - Heidelberg
ER  -