Disease- and sex-specific differences in patients with heart valve disease: a proteome study

Sarah Nordmeyer*, Milena Kraus, Matthias Ziehm, Marieluise Kirchner, Marie Schafstedde, Marcus Kelm, Sylvia Niquet, Mariet Mathew Stephen, Istvan Baczko, Christoph Knosalla, Matthieu-P Schapranow, Gunnar Dittmar, Michael Gotthardt, Martin Falcke, Vera Regitz-Zagrosek, Titus Kuehne*, Philipp Mertins*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number:e202201411
JournalLife Science Alliance
Volume6
Issue number3
DOIs
Publication statusPublished - Mar 2023

Keywords

  • Humans
  • Female
  • Male
  • Proteome
  • Ventricular Remodeling/physiology
  • Proteomics
  • Sex Characteristics
  • Heart Valve Diseases
  • Mitral Valve Insufficiency
  • Aortic Valve Stenosis
  • Fibrosis

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