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Published on: June 29, 2015
Genetic analysis of the plasminogen and coagulation system in mice
1Center for Transgene Technology and Gene Therapy, Vlaams Interuniversitair Instituut voor Biotechnologie, Leuven, Belgium.
Insights
Gene targeting and transfer technologies elucidate the roles of blood clot formation and dissolution systems in cardiovascular diseases and other biological processes. These methods offer insights into treating restenosis and thrombosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Science
Background:
- The blood coagulation and fibrinolytic systems regulate blood clot formation and dissolution.
- These systems are implicated in cardiovascular disorders like thrombosis, atherosclerosis, and restenosis.
- They also play roles in embryonic development, reproduction, wound healing, cancer, and brain function.
Purpose of the Study:
- To review insights gained from gene targeting studies on the biological roles of proteinase systems.
- To discuss the application of adenovirus-mediated gene transfer for studying and treating restenosis and thrombosis.
Main Methods:
- Gene targeting to manipulate proteinase system genetic balance.
- Adenovirus-mediated gene transfer of fibrinolytic genes.
Main Results:
- Gene targeting has provided definitive insights into the biological roles of coagulation and fibrinolytic systems.
- Adenovirus-mediated gene transfer is being explored for therapeutic strategies.
Conclusions:
- Gene manipulation technologies have significantly advanced our understanding of blood clot regulation.
- These technologies hold promise for novel therapeutic approaches to cardiovascular diseases such as restenosis and thrombosis.
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.
