Details

Autor(en) / Beteiligte

• Elkenani, Manar
• Barallobre-Barreiro, Javier
• Schnelle, Moritz
• Mohamed, Belal A
• Beuthner, Bo E
• Jacob, Christoph Friedemann
• Paul, Niels B
• Yin, Xiaoke
• Theofilatos, Konstantinos
• Fischer, Andreas
• Puls, Miriam
• Zeisberg, Elisabeth M
• Shah, Ajay M
• Mayr, Manuel
• Hasenfuß, Gerd
• Toischer, Karl

Titel

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

Ist Teil von

• Frontiers in cardiovascular medicine, 2024-09, Vol.11, p.1398114

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2024

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Patients 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. Left ventricular (LV) myocardial biopsies of PLF-LG (  = 5) and NEF-HG patients (  = 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. 73 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 (  < 0.05). Consistently, immunohistochemical analysis confirmed its extracellular localization in PLF-LG AS LV sections along with an increase in its receptor, CD147, compared to the NEF-HG AS patients. Levels of core ECM proteins, namely collagens and proteoglycans, were comparable between groups. Our study pinpointed novel candidates and processes with potential relevance in the pathophysiology of PLF-LG. The role of CyPA in particular warrants further investigation.