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Frontiers of Medicine

, Volume 11, Issue 1, pp 1–19 | Cite as

Translational initiatives in thrombolytic therapy

  • Melvin E. Klegerman
Review

Abstract

Once thrombi have formed as part of the pathology defining myocardial infarction, ischemic stroke, peripheral arterial disease, deep venous thrombosis or other embolic disorders, the only clinically meaningful thrombolytic agents available for reversing the thrombogenic process are various plasminogen activators. These agents are enzymes that reverse fibrin polymerization underlying the coagulation process by converting endogenous plasminogen to plasmin, which cleaves the fibrin network to form increasingly smaller protein fragments, a process known as fibrinolysis. For the most part, the major clinically used thrombolytics, tissue plasminogen activator, urokinase and streptokinase, as well as the experimentally investigated agent staphylokinase, are the products of recombinant DNA technology, which permits molecular optimization of clinical efficacy. In all cases of molecular optimization and targeting, however, the primary challenge of thrombolytic therapy remains hemorrhagic side effects, which are especially devastating when they occur intracerebrally. Currently, the best strategy to ameliorate this adverse effect is nanoparticulate encapsulation or complexation, and many strategies of this sort are being actively pursued. This review summarizes the variety of targeted and untargeted thrombolytic formulations that have been investigated in preclinical studies.

Keywords

thrombolytics nanomedicine plasminogen activators 

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Notes

Acknowledgements

I wish to acknowledge the contributions of Dr. David D. McPherson and Dr. Susan T. Laing, University of Texas Health Science Center at Houston (UTHealth), who conducted the study shown in Fig. 2. I also wish to thank Steven Kolodziej of the UTHealth pathology department for preparing the negative staining TEM image shown in Fig. 3. The work was supported, in part, by NIH grant (Nos. HL074002, NS047603, and HL059586).

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© Higher Education Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Cardiovascular MedicineUniversity of Texas Health Science Center at Houston (UTHealth)HoustonUSA

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