Calcific aortic valve disease: can targeting endothelial-mesenchymal transition be a new alternative to surgery?-a...

Calcific aortic valve disease (CAVD) is a prevalent and progressive cardiovascular condition, particularly found in the elderly population, characterized by the thickening, calcification, and increased stiffness of the aortic valve leaflets. These structural changes lead to impaired valve function and ultimately contribute to heart failure and increased cardiovascular mortality. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) remain the only effective treatments but are associated with significant risks, high costs, and limited suitability for early-stage or asymptomatic patients. Therefore, the development of non-invasive, disease-modifying therapies is of critical importance. This review aims to summarize current evidence on the role of endothelial-mesenchymal transition (EndMT) in the pathogenesis of CAVD and to explore its potential as a therapeutic target for future non-surgical interventions.

A comprehensive literature search was performed in PubMed, Web of Science, and Embase. Studies related to aortic valve stenosis published between January 1, 2019 and December 20, 2024, as well as all available reports on EndMT published prior to the search date, were included. Only English-language publications were considered, and relevant findings were synthesized to support this review.

Recent studies have highlighted the pivotal role of EndMT in the pathogenesis of CAVD. EndMT contributes to valvular fibrosis, inflammation, and osteogenic differentiation, all of which drive disease progression. Targeting key EndMT-related pathways-such as transforming growth factor-β (TGF-β), Notch, and Wnt-offers promising therapeutic potential. Moreover, combining EndMT-targeted strategies with anti-inflammatory and anti-calcification interventions may enable early-stage intervention, thereby slowing disease progression and reducing reliance on surgical treatments. This review summarizes current understanding of EndMT mechanisms in CAVD and explores emerging therapeutic strategies beyond current surgical options.

CAVD progresses through complex mechanisms involving inflammation, lipid deposition, and osteoblastic differentiation. EndMT has emerged as a key driver of fibrosis and osteogenesis in valve mesenchymal cells, thereby accelerating calcification. However, its regulatory networks and pathway interactions remain incompletely understood. Further research is needed to clarify these mechanisms and develop EndMT-targeted interventions, which may offer new avenues for early diagnosis and treatment of CAVD.