https://orcid.org/0000-0002-8249-5507
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Xingbo Xu, Xiaoying Tan, Baolong Cui, Niels B Paul, Manar Elkenani, Bo E Beuthner, Weichao Li, Belal A Mohamed, Moritz Schnelle, Miriam Puls, Elisabeth M Zeisberg, Michael Zeisberg, Tim Beißbarth, Karl Toischer, Gerd Hasenfuß, Single-nucleus transcriptomics reveals adrenergic and STAT3 signalling in paradoxical low-flow low-gradient-specific cardiomyocyte subclusters: implications for aortic stenosis pathogenesis and treatment, Cardiovascular Research, Volume 120, Issue 13, September 2024, Pages 1505–1507, https://doi.org/10.1093/cvr/cvae137
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Aortic stenosis (AS) is characterized by a narrowed aortic valve, leading to restricted blood flow from the heart. If left untreated, it can progress to heart failure and cardiovascular death.1,2 Notably, normal ejection fraction-high gradient (NEFHG) and paradoxical low-flow low-gradient (PLFLG) represent two distinct manifestations of AS. Notably, PLFLG is more commonly observed in older females and often leads to poorer outcomes following treatment, compared to NEFHG.3,4 In our study, we specifically focused on understanding the underlying molecular mechanisms of NEFHG and PLFLG AS, with our recent findings offering new insights into the molecular differences between these entities. This contributes to a deeper understanding of the pathophysiology of PLFLG, with implications for the development of targeted treatments.
To delve into the molecular differences between these AS types, we collected heart biopsies from patients with PLFLG and NEFHG undergoing transcatheter aortic valve implantation (TAVI) (Figure 1A). These samples were processed using single-nucleus RNA sequencing (snRNA-seq) on the 10X Genomics 3′ Single Cell platform, adhering to the protocols published previously.5 The final dataset consisted of 33 654 nuclei, representing 10 major cell types (Figure 1A). All the patients gave written informed consent prior to study participation, and this study conformed to the principles outlined in the Declaration of Helsinki and was approved by the local Ethics Committee Göttingen.
