Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI...Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen activator (t-PA), accompanied by the oxidative stress and the marked decrease of the main antioxidant—glutathione are fundamental in the bases of elderly pathologies which can cause death. There is some scientific evidence of the relationship between aging, neuro-degenerative diseases, an excessive production of reactive oxygen species and the decrease of proteolysis in brain. The cerebral plasminogen/plasmin system represents the essential proteolytic mechanism that degrades amyloid peptides (β-amyloidosis) for action of plasmin with effectiveness. This physiologic process is being considered as a preventive neurodegenerative mechanism. At the same time, the decrease of glutathione levels in aging entails a decrease of cerebral plasmin activity and a progressive descent of t-PA activity due to a descent in t-PA expression and an increase in PAI production. All of them entail an increment of amyloid beta peptides (Aβ) production and a lower level of their clearance. Both mechanisms, oxidative stress, direct consequence of the oxygenate metabolism of aerobics cells, and changes in the systemic fibrinolysis and cerebral b-amyloidolytic activity, play a very important role in thromboembolic disease, metabolic syndrome—obesity, insulin resistance, hyperglycemia—, type 2 Diabetes Mellitus and Alzheimer’s disease, clinical processes that accompany the aging. In this revision we show the importance of the interaction between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis of the importance of a therapeutic strategy using the inhibition of PAI-1 as a goal, because it is increased in the different aging pathologic processes.展开更多
The purpose of this prospective study is to determine the relative incidence of Alzheimer’s disease in patients treated for at least three years, with sulodexide (n = 46, 76.48 ± 7.02 years old) or acenocoumarol...The purpose of this prospective study is to determine the relative incidence of Alzheimer’s disease in patients treated for at least three years, with sulodexide (n = 46, 76.48 ± 7.02 years old) or acenocoumarol (n = 47, 78.21 ± 6.66 years old) in order to prevent primary and secondary venous thromboembolism and atherothrombotic disease. In the sulodexide group, there was an apparent prevention of cognitive and behavioural impairment (relative incidence: 2.02) compared with acenocoumarol group (relative incidence: 4.86). The favourable results in sulodexide group may be related to their pharmacodynamic actions of inhibition of PAI-1, which may interfere with the pathogenesis of Alzheimer’s disease, and to the role of glutathione and PAI-1 in the β-amyloid system in the brain.展开更多
文摘Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen activator (t-PA), accompanied by the oxidative stress and the marked decrease of the main antioxidant—glutathione are fundamental in the bases of elderly pathologies which can cause death. There is some scientific evidence of the relationship between aging, neuro-degenerative diseases, an excessive production of reactive oxygen species and the decrease of proteolysis in brain. The cerebral plasminogen/plasmin system represents the essential proteolytic mechanism that degrades amyloid peptides (β-amyloidosis) for action of plasmin with effectiveness. This physiologic process is being considered as a preventive neurodegenerative mechanism. At the same time, the decrease of glutathione levels in aging entails a decrease of cerebral plasmin activity and a progressive descent of t-PA activity due to a descent in t-PA expression and an increase in PAI production. All of them entail an increment of amyloid beta peptides (Aβ) production and a lower level of their clearance. Both mechanisms, oxidative stress, direct consequence of the oxygenate metabolism of aerobics cells, and changes in the systemic fibrinolysis and cerebral b-amyloidolytic activity, play a very important role in thromboembolic disease, metabolic syndrome—obesity, insulin resistance, hyperglycemia—, type 2 Diabetes Mellitus and Alzheimer’s disease, clinical processes that accompany the aging. In this revision we show the importance of the interaction between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis of the importance of a therapeutic strategy using the inhibition of PAI-1 as a goal, because it is increased in the different aging pathologic processes.
文摘The purpose of this prospective study is to determine the relative incidence of Alzheimer’s disease in patients treated for at least three years, with sulodexide (n = 46, 76.48 ± 7.02 years old) or acenocoumarol (n = 47, 78.21 ± 6.66 years old) in order to prevent primary and secondary venous thromboembolism and atherothrombotic disease. In the sulodexide group, there was an apparent prevention of cognitive and behavioural impairment (relative incidence: 2.02) compared with acenocoumarol group (relative incidence: 4.86). The favourable results in sulodexide group may be related to their pharmacodynamic actions of inhibition of PAI-1, which may interfere with the pathogenesis of Alzheimer’s disease, and to the role of glutathione and PAI-1 in the β-amyloid system in the brain.
