Hydrogen Peroxide Promotes Aging-Related Platelet Hyperactivation and Thrombosis

• DOI: 10.1161/circulationaha.112.000966
• Publication Date: 2013-02-21T07:03:39Z
• Authors: Sanjana Dayal; Katina M. Wilson; David G. Motto; Francis J. Miller; Anil K. Chauhan; Steven R. Lentz
• Keywords: GPX1; NAD(P)H oxidase

Background— The incidence of thrombotic events increases during aging, but the mechanisms are not well understood. To investigate prothrombotic role oxidative stress we tested hypothesis that aged mice overexpressing antioxidant enzyme glutathione peroxidase-1 (Gpx1) protected from experimental thrombosis. Methods and Results— Susceptibility to carotid artery thrombosis was first examined in wild-type C57BL/6J mice. After photochemical injury artery, time stable occlusion significantly shorter 12- 18-month-old compared with 4-month-old ( P <0.01). Unlike mice, transgenic Gpx1 (Gpx1 Tg) did exhibit shortened times at 12 or 18 months age. Wild-type also exhibited increased susceptibility venous after inferior vena cava ligation age <0.05 versus 4 age). Tg were this aging-related enhanced Age-dependent platelet hyperactivation, evidenced by hydrogen peroxide, fibrinogen binding, activation receptor αIIbβ3, observed thrombin-activated platelets <0.05). Enhanced responses prevented polyethylene glycol–catalase apocynin, an inhibitor NADPH oxidase. Aged displayed intraplatelet expression p47 phox superoxide dismutase-1, suggesting a mechanistic pathway for peroxide generation. Conclusions— Our findings demonstrate is key mediator hyperactivity