Biomedical Engineering Reference
In-Depth Information
Table 8.1
Cardiovascular disorders for which gene therapy is being considered
Genetic cardiovascular disorders
Familial hypercholesterolemia
Hypertension
Familial hypertrophic cardiomyopathy
Long Q-T syndrome
Genetic factors in coronary heart disease
Acquired cardiovascular disease
Coronary artery disease/angina pectoris
Ischemic heart disease/myocardial infarction
Congestive heart failure and cardiomyopathy
Pulmonary hypertension
Cardiac conduction disturbances
Gene therapy and cardiac transplantation
Peripheral arterial disease
Prevention of atherosclerosis
Prevention of restenosis after angioplasty
Maintaining the patency of vascular grafts
Intermittent claudication
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Techniques of Gene Transfer to the Cardiovascular System
Once an appropriate molecular target has been identified, the cellular target of the
proposed genetic manipulation must be chosen. Although this usually means the
cell type most intimately involved in the disease process, it can also be a neighbor-
ing cell type or an organ at a distance from the site of lesion. Local delivery of
genes to the sites of disease is a salient feature of cardiovascular gene therapy.
Various target genes and methods of gene transfer have been considered and
investigated. Special techniques have been developed to target certain areas within
the cardiovascular system and these include direct injection, percutaneous translu-
minal approaches and special catheters. Gene transfer for cardiovascular diseases
can be done ex vivo or in vivo. Ex vivo modification of endothelial and vascular
smooth muscle cells followed by implantation of the cells seeded on prosthetic
graft material or onto luminal surface of native vessels has been shown to be fea-
sible and local or systemic delivery of a transgene can be accomplished. However,
gene transfer is cumbersome and inefficient by this approach. In vivo gene transfer
is preferred for the cardiovascular system.
Direct Plasmid Injection into the Myocardium
A gene can be transferred to the myocardium by direct injection of a plasmid
(a circular, double-stranded unit of DNA). A special plasmid that could transfer a
gene for vascular endothelial growth factor (VEGF), which promotes angiogenesis,
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