Aging-related alterations in mechanistic target of rapamycin signaling promote platelet hyperreactivity and thrombosis.

Background: Aging is an independent risk factor for the development of cardiovascular, thrombotic, and other chronic diseases. However, mechanisms of platelet hyperactivation in aging remain poorly understood.

Objectives: Here, we examine whether and how aging alters intracellular signaling in platelets to support platelet hyperactivity and thrombosis.

The predominant PAR4 variant in individuals of African ancestry worsens murine and human stroke outcomes.

Protease-activated receptor 4 (PAR4) (gene F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency is more common in Black individuals, and Black individuals have a higher incidence of ischemic stroke than White individuals. However, it is not known whether the A allele is responsible for worse stroke outcomes.