TY - JOUR
T1 - Disease- and sex-specific differences in patients with heart valve disease
T2 - a proteome study
AU - Nordmeyer, Sarah
AU - Kraus, Milena
AU - Ziehm, Matthias
AU - Kirchner, Marieluise
AU - Schafstedde, Marie
AU - Kelm, Marcus
AU - Niquet, Sylvia
AU - Stephen, Mariet Mathew
AU - Baczko, Istvan
AU - Knosalla, Christoph
AU - Schapranow, Matthieu-P
AU - Dittmar, Gunnar
AU - Gotthardt, Michael
AU - Falcke, Martin
AU - Regitz-Zagrosek, Vera
AU - Kuehne, Titus
AU - Mertins, Philipp
N1 - Acknowledgements
We would like to thank Alireza Khasheei (clinical imaging) for technical assistance and Manuela Bauer for her support as a study nurse. This work was supported by the German Federal Ministry of Education and Research (grant numbers 031A427A, 031A427B, 031A427C, 031A427D, and 01ZZ1802H), the ERA-CVD (SICVALVES), the CRC1470, and the European Commission under the H2020 Program (Grant No. 689617, Brussels, Belgium). M Kelm is a participant in the Charité Digital Clinician Scientist Program funded by the Deutsche Forschungsgemeinschaft (DFG). M Schafstedde is a participant in the BIH-Charité Junior Digital Clinician Scientist Program funded by the Charité-Universitätsmedizin, Berlin, the Berlin Institute of Health. I Baczko was supported by the Ministry of Human Capacities, Hungary (20391-3/2018/FEKUSTRAT). This work was also supported by the DFG (German Research Foundation) Grant SFB-1470, project Z03 (to T Kuehne), and B05 (to P Mertins).
© 2023 Nordmeyer et al.
PY - 2023/3
Y1 - 2023/3
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.
AB - 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.
KW - Humans
KW - Female
KW - Male
KW - Proteome
KW - Ventricular Remodeling/physiology
KW - Proteomics
KW - Sex Characteristics
KW - Heart Valve Diseases
KW - Mitral Valve Insufficiency
KW - Aortic Valve Stenosis
KW - Fibrosis
UR - https://pubmed.ncbi.nlm.nih.gov/36627164
U2 - 10.26508/lsa.202201411
DO - 10.26508/lsa.202201411
M3 - Article
C2 - 36627164
SN - 2575-1077
VL - 6
JO - Life Science Alliance
JF - Life Science Alliance
IS - 3
M1 - :e202201411
ER -