Plasminogen activation: biochemistry, physiology, and therapeutics

Area of Science:

• Biochemistry
• Molecular Biology
• Physiology

Background:

• The plasmin system, comprising plasminogen, plasminogen activators (PAs), and inhibitors, is crucial for fibrinolysis.
• Plasminogen activators include urokinase (uPA), tissue plasminogen activator (tPA), and streptokinase.
• This system plays roles in physiological processes and pathological conditions like tumor invasion and thromboembolism.

Purpose of the Study:

• To review the biochemical properties of the plasmin system components.
• To discuss the involvement of the plasmin system in various physiological and pathological processes.
• To highlight advancements in thrombolytic therapy using plasminogen activators.

Main Methods:

• Literature review of biochemical properties of plasminogen, PAs, and inhibitors.
• Analysis of studies on the mechanism of fibrinolysis in human plasma.
• Evaluation of newly developed thrombolytic agents.

Main Results:

• Recent studies suggest tPA is a primary initiator of fibrinolysis, with regulation occurring at the tPA level.
• A model for the initiation and regulation of plasma fibrinolysis has been formulated.
• Newer thrombolytic agents (tPA, pro-uPA, acylated streptokinase-plasminogen complex) demonstrate enhanced properties compared to older ones.

Conclusions:

• The plasmin system is a key regulator of fibrinolysis with implications in health and disease.
• tPA appears to be the main initiator of plasma fibrinolysis, tightly regulated.
• Ongoing research focuses on improving thrombolytic agents through genetic and protein engineering.