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

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 ( 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 ( 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.

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© 2024 Elkenani, Barallobre-Barreiro, Schnelle, Mohamed, Beuthner, Jacob, Paul, Yin, Theofilatos, Fischer, Puls, Zeisberg, Shah, Mayr, Hasenfuß and Toischer.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.