ALDH2 rs671-variant versterkt plaatjesactivatie en arteriële trombose

BACKGROUND:Acute myocardial infarction (AMI) caused by thrombosis is a major cause of mortality. A polymorphism inAldh2gene (rs671) is found in approximately 30% to 50% of East Asians, and it is a risk factor for AMI. This mutation impairs aldehyde dehydrogenase 2 (ALDH2) function, but the effect of ALDH2 on platelet activation and thrombosis is unknown.METHODS:Platelets were isolated from platelet-specificAldh2knockout (Aldh2-/-) and ALDH2E506Kknock-in mice (which corresponds to humanAldh2rs671 gene mutation), as well as from healthy human donors with theAldh2rs671. Arterial thrombosis was measured in a FeCl3-induced thrombosis mouse model. The efficacy of Alda-1, an ALDH2 activator, in mitigating thrombogenesis was measured in ALDH2E506Kmice. Using a murine model of myocardial infarction (MI) model, we analyzed the effects of plateletAldh2on micro-thrombosis and infarct expansion post-MI. In addition, we enrolled 118 patients of differentAldh2rs671 genotypes (GG, GA, and AA) diagnose