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REVIEW: Plasminogen Activator Inhibitor-1 (PAI-1): A Key Factor Linking Fibrinolysis and Age-Related Subclinical and Clinical Conditions
Matteo Cesari,
Marco Pahor,
Raffaele Antonelli Incalzi,
Matteo Cesari
Area di Geriatria, Università Campus Bio-Medico, Rome, Italy
Fondazione “Alberto Sordi”, Rome, Italy
Search for more papers by this authorMarco Pahor
Department of Aging and Geriatric Research, University of Florida – Institute on Aging, Gainesville, FL, USA
Search for more papers by this authorRaffaele Antonelli Incalzi
Area di Geriatria, Università Campus Bio-Medico, Rome, Italy
Fondazione “Alberto Sordi”, Rome, Italy
Search for more papers by this authorMatteo Cesari,
Marco Pahor,
Raffaele Antonelli Incalzi,
Matteo Cesari
Area di Geriatria, Università Campus Bio-Medico, Rome, Italy
Fondazione “Alberto Sordi”, Rome, Italy
Search for more papers by this authorMarco Pahor
Department of Aging and Geriatric Research, University of Florida – Institute on Aging, Gainesville, FL, USA
Search for more papers by this authorRaffaele Antonelli Incalzi
Area di Geriatria, Università Campus Bio-Medico, Rome, Italy
Fondazione “Alberto Sordi”, Rome, Italy
Search for more papers by this authorCorrespondence
Matteo Cesari, M.D., Ph.D., Area di Geriatria, Università Campus Bio-Medico, Via Alvaro del Portillo 5, 00128 Rome, Italy.Tel.: +39 (06) 225411350;Fax: +39 (06) 225411028;E-mail: [email protected]
SUMMARY
Introduction: The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Methods: Narrative review. Results: Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urokinase-type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Conclusions: Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the future.
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