Abstract 12723: Overexpression Of Glutathione Peroxidase-1 Protects Mice From Increased Susceptibility To Experimental Thrombosis With Aging
The incidence of life-threatening thrombotic events such as stroke, myocardial infarction, deep venous thrombosis, and pulmonary embolism increases with age. Despite the established clinical association between aging and thrombosis, very little is known about the mechanisms by which aging increases susceptibility to thrombotic events. In this study, we tested the hypothesis that, like humans, mice exhibit increased susceptibility to thrombosis with aging and examined the protective role of glutathione peroxidase. Susceptibility to carotid artery thrombosis was examined in male C57Bl6/J mice at 4 months, 12 months, or 18 months of age. A total of 7–11 mice were included in each age group. Platelet counts, hematocrit, and baseline blood flow through the carotid artery were similar in all age groups. The time to stable occlusion after photochemical injury (rose bengal and green laser) of the carotid artery was significantly shortened in both 12 months (15.9±3.2 minutes) and 18 months (15.6±3.7 minutes) old mice compared to 4 months old mice (52.5±9.2 minutes, P< 0.01). Since aging is associated with increased oxidative stress, we tested the hypothesis that transgenic mice overexpressing the antioxidant enzyme glutathione peroxidase-1 (Gpx1) are protected from aging-associated increased susceptibility to thrombosis. The time to stable occlusion of the carotid artery in non-transgenic mice was significantly shorter at 12 and 18 months than at 4 months of age, but Gpx1 transgenic mice were protected from this age-induced enhanced susceptibility to thrombosis. These findings suggest that mice develop enhanced susceptibility to thrombosis with advancing age through a mechanism that is mediated by oxidative stress.
- © 2010 by American Heart Association, Inc.