The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi

Abstract

Formation of endogenous thrombi in blood vessels is one of the leading causes of death in our modern life. According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world. For this, a tremendous amount of research has been done in the area of prevention and treatment of these diseases. The classical therapy of these thrombi relies upon the use of antiplatelets, anticoagulants, or even surgeries. Relatively recently, the fibrinolytic enzymes produced by microorganisms, snakes, earthworms, insects, plants, and other organisms are being successfully used in the treatment of blood clots, especially with regard to the direct dissolving action on fibrin in tandem with less cost and side effects in comparison with the first-generation thrombolytic agents, streptokinase and urokinase. Furthermore, recombinant DNA technology has succeeded in improving and decreasing the undesirable effects of the first generation of enzymes. Recombinant PAs or rt-PAs like alteplase, retelase, saruplase, tenecteplase, lanoteplase, and desmoteplase became available in the drug markets with advantages of less binding loci with PAI-1 to avoid degradation while providing faster and more complete reperfusion in a greater number of patients with less risk of bleeding and intracranial hemorrhage. This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.

The evolution of recombinant thrombolytics: Current status and future directions

“…It acts synergistically with antibiotics by liquefying bio-films produced by bacteria to protect themselves from the action of antibiotics indicating its role as a mucus liquefying agent. 4 It was found that in patients with chronic airway diseases, 30 mg of serrapeptase daily for 4 weeks reduced sputum weight and neutrophil count as well as its viscosity and elasticity. 167 Fermented boiled soya beans (natto, part of Japanese diet) release a fibrinolytic substance called nattokinase (NK) (EC 3.4.21.62).…”

“…E-15, is isolated from the intestine of the silkworm Bombyx mori. 4 It is a Zn 2C metalloprotease with a molecule weight of »60 kDa. It helps the silkworms to digest their cocoons but does not affect the living tissue.…”

“…Fibrinolytic enzymes, on the other hand, are used to lyse pre-existing thrombi. 4,5 Enzymes are used as anti-inflammatory agents, digestive aids, mucolytics, thrombolytics, anticoagulants, oncolytics, and antimicrobials for the clinical management of several disorders. 4 Thrombolytic enzymes are mainly serine or metalloproteases having a direct or indirect mode of action for fibrin lysis.…”

“…4,5 Enzymes are used as anti-inflammatory agents, digestive aids, mucolytics, thrombolytics, anticoagulants, oncolytics, and antimicrobials for the clinical management of several disorders. 4 Thrombolytic enzymes are mainly serine or metalloproteases having a direct or indirect mode of action for fibrin lysis. The former includes plasmin-like enzymes such as miniplasmin, micro-plasmin, delta-plasmin, nattokinase (NK), serrapeptase (SP), some snake-venom thrombin-like enzymes (SVTLEs), and some earthworm fibrinolytic enzymes (EFEs), capable of degrading fibrin directly while the latter group is composed of the plasminogen activators that include streptokinase (SK), staphylokinase (SAK), urokinase (u-PA) and tissue-plasminogen activator (t-PA) etc (Table 1).…”

“…6 Microbes from food and non-food sources have been found to be promising producers of such thrombolytic enzymes with Bacillus being the most important genus. 4 Fermented Asian foods have been found to provide a good habitat for the production of such bacterial enzymes. 6 Furthermore, apart from humans and microbes, thrombolytic enzymes have also been reported in animals like vampire bats, snakes and earthworms and more recently in plant lattices.…”