Biomedical Engineering Reference
In-Depth Information
vessels restrict blood flow. DNA-based HGF may be effective for people who do
not respond to sufficiently conventional drugs, balloon catheterization, or surgery.
Maintaining Vascular Patency After Surgery
Within the first year, 15-20% of coronary artery saphenous vein bypass grafts
occlude because of thrombosis or progressive intimal hyperplasia. One strategy to
reduce this complication would be the introduction of antithrombotic or antiprolif-
erative genes in venous bypass grafts before implantation. The success of this
approach requires an efficient DNA delivery system. Further studies will be needed
to determine the long-term effects of this procedure on improvement of vein graft
patency.
Vein graft remodeling results in reduction of the high distensibility of the vessel
wall and provides capability of coping with the arterial blood pressure. This process
involves formation of neointimal layer, which is very susceptible to atherosclerosis.
Up to 50% of the grafts fail within a period of 10 years as a result of this occlusive
disease. An intraoperative antisense approach using oligodeoxynucleotides can
selectively block vascular smooth muscle proliferation and prevent accelerated
atherosclerosis. HJV-liposome oligodeoxynucleotide complexes have been used for
genetic engineering of vein grafts in New Zealand White rabbits. These genetically
modified grafts demonstrate a sustained resistance to diet-induced atherosclerosis.
Thrombosis is a recognized complication of several surgical procedures on the
arteries. Systemic anticoagulation is sometimes used to prevent this complication.
One method relevant to gene therapy approach in such situations is a model for gene
transfer via adventitia using a silastic collar wrapped around rabbit carotid arteries.
The collar serves as a reservoir for the delivery of b-galactosidase marker gene. The
following gene transfer systems were tested in this model: plasmid/liposome com-
plexes, MMLV retroviruses, VSV (vesicular stomatitis virus)-G pseudotyped retro-
viruses, and adenoviruses. There was detectable gene transfer to the arterial wall
including the endothelium with all delivery system. The highest transfer efficiency
(10%) was seen with adenoviral vectors. The advantage of this system is that no
intravascular manipulations are required. This system enables delivery of genes to
the adventitia from an adventitial reservoir to prevent thrombosis during vascular
procedures such as insertion of prostheses and bypass surgery.
Antisense Therapy for Cardiovascular Disorders
Antisense molecules are synthetic segments of DNA or RNA, designed to mirror
specific mRNA sequences and block protein production. The use of antisense drugs
to block abnormal disease-related proteins is referred to as antisense therapeutics.
Synthetic short segments of DNA or RNA are referred to as oligonucleotides. The
literal meaning of this word is a polymer made of few nucleotides. Naturally occurring
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