Building a bypass to last
3 October 2006
Coronary artery bypass grafting remains the most effective treatment of coronary heart disease.
So prolonging the lifespan and quality of the vein graft has been an area of intense investigation by researchers at the Bristol Heart Institute for several years. They have found that covering the vein graft with a porous Dacron sheath, called the external stent or ‘Extent’, prevented wall thickening almost completely in experimental models. Over the ensuing years the basis for this effect has been better understood and the design of the stent so enhanced such that a randomised clinical trial of the Extent in patients having bypass grafts has recently started at the Bristol Heart Institute.
The vein does not adapt well to its new role as an artery
Thickening of the veins is caused mainly by smooth muscle cell growth (the cells in the graft divide and multiply), so drugs that prevent this may also prevent vein thickening. Promising pre-clinical studies have focused on the use of drugs that have a potent ability to prevent smooth muscle cell growth, such as drugs commonly used in the treatment of cancer or transplant rejection. These have been shown to inhibit vein-graft disease in experimental models. Future research in this area is directed at refining drug delivery with the hope that these drugs may be entered into clinical trials in the next few years.
Finally, a (non-harmful) virus has been engineered to introduce a gene called TIMP-3 that not only reduces movement of smooth muscle cells to the vein wall, but also destroys those already present. Local application of this virus has reduced vein-wall thickening and it is anticipated that human trials could start within a few years.
Can the heart grow new blood vessels?
One method of improving blood supply to the heart that does not involve surgery is to get the heart to grow its own new blood vessels – a process known as angiogenesis. Certain genes encode proteins called growth factors that can stimulate formation of new blood vessels. Recent research, using experimental models, has shown that injection of such genes can stimulate angiogenesis. However, to achieve that, genes for several different growth factors are required, since they stimulate different parts of blood vessel development. Some growth factors stimulate vessel ‘sprouting’, whilst others cause support cells to surround the newly growing vessel, before being replaced finally by smooth muscle cells. Researchers at the Bristol Heart Institute are investigating which combination of these growth factors is most beneficial.