Enoyl coenzyme a hydratase 1 attenuates aortic valve calcification by suppressing Runx2 via Wnt5a/Ca²⁺ pathway

Area of Science:

• Cardiovascular Biology
• Molecular Mechanisms of Disease
• Biochemistry

Background:

• Calcific aortic valve disease (CAVD) presents high morbidity and mortality.
• Limited therapeutic options exist for CAVD.
• The role of Enoyl coenzyme A hydratase 1 (ECH1) in CAVD is largely unknown.

Purpose of the Study:

• To investigate the function and therapeutic potential of ECH1 in CAVD.
• To elucidate the underlying mechanisms of ECH1 action in CAVD.
• To explore ECH1 as a potential therapeutic target for CAVD.

Main Methods:

• Single-cell sequencing to analyze ECH1 expression in valve interstitial cells.
• In vitro and in vivo experiments using ApoE-/- mice models.
• Modulation of ECH1 expression (overexpression and silencing).
• Wnt signaling pathway analysis (Wnt5a, CHIR99021).
• Chromatin immunoprecipitation (ChIP) and luciferase assays to assess Runx2 binding.

Main Results:

• ECH1 expression is significantly reduced in calcific aortic valves.
• ECH1 overexpression reduced aortic valve calcification in a mouse model.
• ECH1 silencing exacerbated aortic valve calcification.
• ECH1 suppressed Wnt signaling, including Wnt5a and Ca2+ regulation.
• ECH1 prevented Runx2 binding to osteopontin and osteocalcin promoters.

Conclusions:

• ECH1 plays a protective role against CAVD development.
• ECH1 exerts anti-calcific effects by suppressing the Wnt signaling pathway.
• Targeting ECH1 represents a potential therapeutic strategy for preventing CAVD.