Valvular & structural heart disease
Aortic Valve Calcification Is Induced by the Loss of ALDH1A1 and Can Be Prevented by Agonists of Retinoic Acid Receptor Alpha: Preclinical Evidence for Drug Repositioning
Authors' conclusion
These results show that ALDH1A1 is downregulated in calcified valves, hence promoting VIC transition into an osteoblastic phenotype.
Study context
- Population
- Explanted human aortic valves (patients and organ donor hearts); rat subcutaneous bovine pericardium implantation and juvenile sheep xenograft aortic valve replacement models
- Comparison
- Calcified (bicuspid and tricuspid) vs control valves; all-trans retinoic acid for calcification prevention
Methodological detailshuman valvular interstitial cells (VIC) cultures, 2 animal models
- Human VIC cultures
- 2 animal models
Main finding
As reported in the abstract
- ALDH1A1 was the most downregulated gene in VIC from calcified vs control valves
- In human VIC, ALDH1A1 expression is downregulated by TGF-β in a SMAD2/3-dependent manner
- ALDH1A1 inhibition promotes an osteoblast-like VIC phenotype and increases calcium deposition via inhibition of retinoic acid receptor alpha signalling
- Retinoid treatment of VIC decreases calcium deposition and attenuates VIC osteoblast activity
- All-trans retinoic acid inhibits calcification of aortic BPV in both in vivo models and improves aortic valve echocardiographic parameters in the sheep xenograft model
Original publication
Aortic Valve Calcification Is Induced by the Loss of ALDH1A1 and Can Be Prevented by Agonists of Retinoic Acid Receptor Alpha: Preclinical Evidence for Drug Repositioning. Circulation. Published 24 February 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →