The Aldehyde Dehydrogenase 2 rs671 Variant Enhances Platelet Activation and Arterial Thrombosis
Authors' conclusion
The Aldh2 rs671 variant, which impairs ALDH2 function, increases platelet activation and thrombus formation in vivo through aldehyde accumulation and ROS buildup.
Study context
- Population
- Mouse models; healthy human donors with Aldh2 rs671; ST elevation myocardial infarction (STEMI) patients of different rs671 genotypes (GG, GA, AA)
- Participants
- 118 STEMI patients
- Comparison
- Aldh2 rs671 variant / Aldh2 deficiency vs wild-type
Main finding
As reported in the abstract
- Aldh2-/- and ALDH2E506K platelets: enhanced agonist-induced aggregation, ATP release, integrin αIIbβ3 activation, P-selectin release, spreading and clot retraction
- Human platelets with Aldh2 rs671 variant: increased activation
- Aldh2 mutation or platelet-specific knockout exacerbated thrombus formation in mouse thrombosis model
- Alda-1 (ALDH2 activator) reduced thrombosis in ALDH2E506K mice
- Platelets lacking Aldh2: more reactive oxygen species (ROS), less nitric oxide (NO) than wild-type; more susceptible to activation by aldehydes
- Platelets lacking Aldh2: increased mitophagy and hyperactivity; ACAD10 mediated some ALDH2 effects on mitophagy
- Mice lacking Aldh2: increased micro-thrombosis and MI expansion
- STEMI patients with rs671 variant: elevated plasma platelet activation and thrombus markers
Original publication
The Aldehyde Dehydrogenase 2 rs671 Variant Enhances Platelet Activation and Arterial Thrombosis. Circulation. Published 6 February 2026. doi:10.
Summarised from the published abstract; every number is checked against it