Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy

Abstract

Thrombosis, a major cause of deaths in this modern era responsible for 31% of all global deaths reported by WHO in 2017, is due to the aggregation of fibrin in blood vessels which leads to myocardial infarction or other cardiovascular diseases (CVDs). Classical agents such as anti-platelet, anti-coagulant drugs or other enzymes used for thrombosis treatment at present could leads to unwanted side effects including bleeding complication, hemorrhage and allergy. Furthermore, their high cost is a burden for patients, especially for those from low and middle-income countries. Hence, there is an urgent need to develop novel and low-cost drugs for thrombosis treatment. Fibrinolytic enzymes, including plasmin like proteins such as proteases, nattokinase, and lumbrokinase, as well as plasminogen activators such as urokinase plasminogen activator, and tissue-type plasminogen activator, could eliminate thrombi with high efficacy rate and do not have significant drawbacks by directly degrading the fibrin. Furthermore, they could be produced with high-yield and in a cost-effective manner from microorganisms as well as other sources. Hence, they have been considered as potential compounds for thrombosis therapy. Herein, we will discuss about natural mechanism of fibrinolysis and thrombus formation, the production of fibrinolytic enzymes from different sources and their application as drugs for thrombosis therapy.

Citric acid-mediated green synthesis of selenium nanoparticles: antioxidant, antimicrobial, and anticoagulant potential applications

“…To treat thrombosis, various antithrombotic medicines are available on the market. Antiplatelet medications prevent platelet activation or aggregation, while anticoagulant medications prevent fibrin production, but fibrinolytic treatments break down fibrin formation [ 62 ]. Using biologically produced AgNPs compared with selective active molecules has recently been demonstrated to be successful anticoagulant properties and requires less than active molecules [ 41 , 63 ].…”

Thrombus-Targeting Polymeric Nanocarriers and Their Biomedical Applications in Thrombolytic Therapy

“…Consequently, existing strategies for thrombus treatment are primarily aimed at platelets and fibrin networks. For example, when the nanocarriers are targeted to reach the thrombus site, the plasminogen activator that they release can activate the plasminogen near the thrombus to become plasmin ( Altaf et al, 2021 ), and then dissolve the cross-linked bonds between fibrin, destroy its network structure, and thus dissolve the blood clot ( Figure 2 ; Collen and Lijnen, 2005 ; Hassanpour et al, 2020 ).…”

cRGD Urokinase Liposomes for Thrombolysis in Rat Model of Acute Pulmonary Microthromboembolism

“…9 Thrombolytic drugs, such as urokinase, activating plasminogen into plasmin to dissolve fibrin and then breaking down thrombosis, are the first choice for reperfusion therapy. However, these thrombolytic drugs have side effects, such as systemic fibrinolysis, hemorrhage, short half-life et al 10 Incomplete thrombolysis, involved in side effects, which leads to distal vascular embolism, is also one of the causes of pulmonary microthromboembolism. Therefore, upgrading thrombolytic drugs is one of the keys to optimize the treatment of pulmonary thromboembolism.…”