Journal
AGE
Volume 32, Issue 1, Pages 109-121Publisher
SPRINGER
DOI: 10.1007/s11357-009-9119-y
Keywords
Aging; Estrogen receptors; Microparticles; Mitochondria; Platelet energy metabolism; Procoagulant activity
Categories
Funding
- National Institutes of Health [NHLBI HL78638, NHLBI HL089542]
- National Institute of Aging [AG 21201]
- American Heart Association [AHA 08-30503Z]
- Mayo Foundation
- Division of Intramural Research of the NIEHS
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL089542] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES070065] Funding Source: NIH RePORTER
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Platelets derived from aged (reproductively senescent) female mice with genetic deletion of estrogen receptor beta (beta ER) are more thrombogenic than those from age-matched wild-type (WT) mice. Intracellular processes contributing to this increased thrombogenicity are not known. Experiments were designed to identify subcellular localization of estrogen receptors and evaluate both glycolytic and mitochondrial energetic processes which might affect platelet activation. Platelets and blood from aged (22-24 months) WT and estrogen receptor beta knockout (beta ERKO) female mice were used in this study. Body, spleen weight, and serum concentrations of follicle-stimulating hormone and 17 beta-estradiol were comparable between WT and beta ERKO mice. Number of spontaneous deaths was greater in the beta ERKO colony (50% compared to 30% in WT) over the course of 24 months. In resting (nonactivated) platelets, estrogen receptors did not appear to colocalize with mitochondria by immunostaining. Lactate production and mitochondrial membrane potential of intact platelets were similar in both groups of mice. However, activities of NADH dehydrogenase, cytochrome bc (1) complex, and cytochrome c oxidase of the electron transport chain were reduced in mitochondria isolated from platelets from beta ERKO compared to WT mice. There were a significantly higher number of phosphatidylserine-expressing platelet-derived microvesicles in the plasma and a greater thrombin-generating capacity in beta ERKO compared to WT mice. These results suggest that deficiencies in beta ER affect energy metabolism of platelets resulting in greater production of circulating thrombogenic microvesicles and could potentially explain increased predisposition to thromboembolism in some elderly females.
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