Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.

ABSTRACT:

Aims

Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.

Methods and results

An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The A

SUBMITTER: Iqbal F 

PROVIDER: S-EPMC9991042 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature