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Review

PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target

1
Biochemistry Department, Faculty of Science, Jeddah University, Jeddah 23235, Saudi Arabia
2
Division of Cardiovascular & Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds LS2 9JT, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Manfredi Rizzo
Int. J. Mol. Sci. 2021, 22(6), 3170; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063170
Received: 25 February 2021 / Revised: 16 March 2021 / Accepted: 17 March 2021 / Published: 20 March 2021
(This article belongs to the Special Issue Molecular Pathways for Vascular Risk in Diabetes)
Hypofibrinolysis is a key abnormality in diabetes and contributes to the adverse vascular outcome in this population. Plasminogen activator inhibitor (PAI)-1 is an important regulator of the fibrinolytic process and levels of this antifibrinolytic protein are elevated in diabetes and insulin resistant states. This review describes both the physiological and pathological role of PAI-1 in health and disease, focusing on the mechanism of action as well as protein abnormalities in vascular disease with special focus on diabetes. Attempts at inhibiting protein function, using different techniques, are also discussed including direct and indirect interference with production as well as inhibition of protein function. Developing PAI-1 inhibitors represents an alternative approach to managing hypofibrinolysis by targeting the pathological abnormality rather than current practice that relies on profound inhibition of the cellular and/or acellular arms of coagulation, and which can be associated with increased bleeding events. The review offers up-to-date knowledge on the mechanisms of action of PAI-1 together with the role of altering protein function to improve hypofirbinolysis. Developing PAI-1 inhibitors may form for the basis of future new class of antithrombotic agents that reduce vascular complications in diabetes. View Full-Text
Keywords: plasminogen activator inhibitor 1 (PAI-1); PAI-1 inhibitors; diabetes; hypofibrinolysis; cardiovascular disease; therapeutics plasminogen activator inhibitor 1 (PAI-1); PAI-1 inhibitors; diabetes; hypofibrinolysis; cardiovascular disease; therapeutics
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MDPI and ACS Style

Altalhi, R.; Pechlivani, N.; Ajjan, R.A. PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target. Int. J. Mol. Sci. 2021, 22, 3170. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063170

AMA Style

Altalhi R, Pechlivani N, Ajjan RA. PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target. International Journal of Molecular Sciences. 2021; 22(6):3170. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063170

Chicago/Turabian Style

Altalhi, Rawan, Nikoletta Pechlivani, and Ramzi A. Ajjan 2021. "PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target" International Journal of Molecular Sciences 22, no. 6: 3170. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063170

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