Cellular and extracellular proteomic profiling of paradoxical low-flow low-gradient aortic stenosis myocardium

Autor: Manar Elkenani, Javier Barallobre-Barreiro, Moritz Schnelle, Belal A. Mohamed, Bo E. Beuthner, Christoph Friedemann Jacob, Niels B. Paul, Xiaoke Yin, Konstantinos Theofilatos, Andreas Fischer, Miriam Puls, Elisabeth M. Zeisberg, Ajay M. Shah, Manuel Mayr, Gerd Hasenfuß, Karl Toischer
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Cardiovascular Medicine, Vol 11 (2024)
Druh dokumentu: article
ISSN: 2297-055X
DOI: 10.3389/fcvm.2024.1398114
Popis: AimsPatients with severe aortic stenosis (AS), low transvalvular flow (LF) and low gradient (LG) with normal ejection fraction (EF)—are referred to as paradoxical LF-LG AS (PLF-LG). PLF-LG patients develop more advanced heart failure symptoms and have a worse prognosis than patients with normal EF and high-gradient AS (NEF-HG). Despite its clinical relevance, the mechanisms underlying PLF-LG are still poorly understood.MethodsLeft ventricular (LV) myocardial biopsies of PLF-LG (n = 5) and NEF-HG patients (n = 6), obtained during transcatheter aortic valve implantation, were analyzed by LC-MS/MS after sequential extraction of cellular and extracellular matrix (ECM) proteins using a three-step extraction method. Proteomic data are available via ProteomeXchange with identifier PXD055391.Results73 cellular proteins were differentially abundant between the 2 groups. Among these, a network of proteins related to muscle contraction and arrhythmogenic cardiomyopathy (e.g., cTnI, FKBP1A and CACNA2D1) was found in PLF-LG. Extracellularly, upregulated proteins in PLF-LG were related to ATP synthesis and oxidative phosphorylation (e.g., ATP5PF, COX5B and UQCRB). Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p
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