Abstract
The blood coagulation and the fibrinolytic (or plasminogen/plasmin) systems determine the balance between the formation and dissolution of blood clots, but in addition contribute to the pathogenesis of various cardiovascular disorders such as thrombosis, atherosclerosis and restenosis. Furthermore, they participate in a variety of other (patho)biological processes such as embryonic development, reproduction, wound healing, cancer and brain function. Two recently developed technologies, gene targeting and gene transfer, that allow to manipulate the genetic balance of these proteinase systems in a controllable manner have allowed to more definitively elucidate the biological role of these systems. This review summarizes the insights that have been obtained from the gene targeting studies and discusses the use of adenovirus-mediated transfer of fibrinolytic genes to study and possibly to develop novel strategies for the treatment of restenosis and thrombosis.
MeSH terms
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Animals
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Arteriosclerosis / genetics
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Arteriosclerosis / physiopathology
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Blood Coagulation / genetics*
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Blood Coagulation Disorders / genetics
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Blood Coagulation Disorders / physiopathology
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Blood Coagulation Factors / genetics*
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Blood Coagulation Factors / physiology
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Blood Vessels / injuries
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Embryonic and Fetal Development / physiology
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Enzyme Activation
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Fibrinolysin / genetics*
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Fibrinolysin / physiology
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Fibrinolysis / genetics*
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Gene Targeting
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Humans
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Mice
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Mice, Knockout
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Mice, Transgenic
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Plasminogen / genetics*
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Plasminogen / physiology
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / physiology
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Recombinant Fusion Proteins / metabolism
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Tissue Plasminogen Activator / genetics
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Tissue Plasminogen Activator / physiology
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Transfection
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Wound Healing / genetics
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Wound Healing / physiology
Substances
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Blood Coagulation Factors
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Plasminogen Activator Inhibitor 1
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Recombinant Fusion Proteins
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Plasminogen
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Tissue Plasminogen Activator
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Fibrinolysin