title: Zebrafish model of photochemical thrombosis for translational research and thrombolytic screening in vivo.
abstract: Acute thromboembolic diseases remain the major global cause of death or disability. Although an array of thrombolytic and antithrombotic drugs has been approved to treat or prevent thromboembolic diseases, many more drugs that target specific clotting mechanisms are under development. Here a novel zebrafish model of photochemical thrombosis is reported and its prospective application for the screening and preclinical testing of thrombolytic agents in vivo is demonstrated. Through photochemical excitation, a thrombus was induced to form at a selected section of the dorsal aorta of larval zebrafish, which had been injected with photosensitizers. Such photochemical thrombosis can be consistently controlled to occlude partially or completely the targeted blood vessel. Detailed mechanistic tests indicate that the zebrafish model of photochemical thrombosis exhibits essential features of classical coagulation and a thrombolytic pathway. For demonstration, tissue plasminogen activator (tPA), a clinically feasible thrombolytic agent, was shown to effectively dissolve photochemically induced blood clots. In light of the numerous unique advantages of zebrafish as a model organism, our approach is expected to benefit not only the development of novel thrombolytic and antithrombotic strategies but also the fundamental or translational research targeting hereditary thrombotic or coagulation disorders.
authors.affiliation: Department of Applied Chemistry and Institute of Molecular Science, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Lee
authors.affiliation: Department of Applied Chemistry and Institute of Molecular Science, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: Yi-Cyun
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Department of Applied Chemistry and Institute of Molecular Science, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: Jia-Wen
authors.initials: JW
authors.lastname: Hsu
authors.affiliation: Department of Emergency Medicine and Cardiovascular Center, National Taiwan University Hospital and College of Medicine, Taipei, 100, Taiwan.
authors.forename: Wei-Tien
authors.initials: WT
authors.lastname: Chang
authors.affiliation: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 300, Taiwan.
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
authors.affiliation: Department of Applied Chemistry and Institute of Molecular Science, National Chiao Tung University, Hsinchu, 300, Taiwan.
authors.forename: Ian
authors.initials: I
authors.lastname: Liau
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007814:Larva; D007834:Lasers; D017319:Photosensitizing Agents; D012395:Rose Bengal / Q000633:toxicity; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D005343:Fibrinolytic Agents; D017319:Photosensitizing Agents; D012395:Rose Bengal; D010959:Tissue Plasminogen Activator
keywords: drug screen; photochemistry; thrombolysis; thrombosis; zebrafish