Monday October 25 2010
Margatoxin is found in the sting of the American bark scorpion
Scorpion venom “could prevent bypass failures”, according to the Daily Mail, which says the toxin can help keep veins clear after heart bypass surgery. According to the newspaper, a study has found that ‘margatoxin’, produced by the Central American bark scorpion, could stop the scarring that can block grafted blood vessels after surgery.
The laboratory research in human and mouse cells has identified how particular chemical channels in the walls of cells govern the formation of scar tissue in blood vessels. Margatoxin was found to block these channels, and it appears to prevent the multiplication of the smooth muscle cells that cause the scars.
However, it is a leap to suggest that the toxin is a new method of preventing failure of bypass grafts. This early research has not tested the effects of the toxin in live animals, let alone humans, and graft failures are not always caused by scarring in the blood vessels. The lead researcher also says that the toxin would not be suitable in an oral, injectable or inhalable treatment anyway. This highlights how much work still needs to be done.
Where did the story come from?
The study was carried out by researchers from the University of Leeds and was funded by the British Heart Foundation, the Medical Research Council, Nuffield Hospital in Leeds and the Wellcome Trust. The study was published in the peer-reviewed medical journal Cardiovascular Research.
Newspapers have generally glossed over the methods of the research. Few of them note the important point that this is very early stage research carried out in human and mouse cells in a laboratory. The overly optimistic headlines may lead readers to believe that a drug that ‘prevents bypass failures’ has been developed and tested in humans. This is far from the truth, as this was preliminary research, which actually focused on the cellular processes involved in forming blood vessel scars.
The lead researcher is quoted by the Daily Mail as saying that the toxin is likely to be unsuitable for use in a drug that would be swallowed, injected or inhaled, but it could perhaps be sprayed onto the vein before it is transplanted. This has not been researched any further yet.
What kind of research was this?
Coronary artery bypass graft (CABG) surgery is a major operation in which arteries or veins from another site in the body are grafted onto those of the heart to bypass diseased vessels. It has saved many lives. One potential complication of heart surgery (particularly stent insertions and bypass grafts) is ‘neoinitimal hyperplasia’, the development of scar tissue in the blood vessels immediately around the site of the procedure. It is caused by the migration and growth of smooth muscle cells inside the new inner structure, which can eventually restrict blood flow in the vessel.
A number of different mechanisms have been found to inhibit the migration of these cells. In this laboratory study, researchers further examined the effects of different substances on healthy vessel tissue and at the sites of scar tissue in blood vessels from patients and mice. They were particularly interested in the role of calcium- and potassium-transporting channels found in the cell walls, including one called Kv1.3.
What did the research involve?
The researchers compared different types of smooth muscle cells found in mouse aortas, to determine the characteristics of the normal cells and those that proliferate heavily, potentially leading to scarring. They wanted to profile the types of channels in these cells and see which ones may have been predominant in the different types of muscle cell.
Human and mouse smooth muscle cells were cultured, then injured with a 0.3 mm wide scrape across each culture. Cells usually respond to this type of ‘injury’ by regrowing into the wound. For 48 hours the researchers treated the cells with chemicals that block the actions of the Kv1.3 ion channels. After this, the researchers counted the number of cells in the wound. The two different compounds tested were called margatoxin and correolide compound C. Margatoxin is found within the venom of certain types of scorpion.
Further experiments were conducted on cultured veins (from human legs) rather than just on the muscle cells. In these experiments, the development of scarring was again compared in samples exposed to margatoxin and correolide compound C.
What were the basic results?
One particular type of potassium channel (called Kv1.3) was found to be involved in the change of smooth muscle cells to the type that could reproduce (proliferating type). This channel was active and abundant within the smooth muscle cells in vessels, and was highly concentrated in scarred human veins.
Exposing cultured cells to margatoxin and correolide compound C, both of which can block the Kv1.3 potassium channels, reduced their response to injury, although this reduction was smaller in human cells than in mouse cells. The response to injury in this case was determined by the number of cells that grew into the scrape on the cell culture.
In similar experiments on human veins, margatoxin and correolide compound C both reduced the formation of scar tissue.
How did the researchers interpret the results?
The researchers conclude that the Kv1.3 ion-transporting channels are important in the proliferation of smooth muscle cells within the vessels. They say that the results suggest a potential role for substances that can block Kv1.3 as ‘suppressors of neointimal hyperplasia’ (the potentially-dangerous development of scar tissue in the vessels).
This laboratory research has detailed the involvement of a particular potassium channel in the cell wall of smooth muscle cells in mouse and human blood vessels. These channels have been linked with migration and reproduction of the muscle cells, and are therefore implicated in the development of scar tissue in the cardiac vessels following surgery. The study investigated the effects of blocking the Kv1.3 channels with different substances. One of the two compounds studied here, margatoxin, is found in the venom of a scorpion.
The news coverage of this study implies that an extract of scorpion venom can prevent the failure of bypass grafts. This is misleading and not supported by the early stage of this research, which focused on the cellular processes behind blood vessel scarring rather than developing margatoxin into a medicine. The researchers themselves do not emphasise the potential of the margatoxin as a treatment per se, concluding that they have determined a role for Kv1.3 potassium channels in the migration of vascular smooth muscle cells. It must also be remembered that there are a number of reasons why cardiac surgery of this kind may fail, with neoinitimal hyperplasia being only one of them.
It is very premature to imply that this research has discovered a treatment for a potentially fatal complication of heart surgery. The Daily Mail quotes the lead researcher as saying that margatoxin would not be suitable for use in a drug that could be swallowed, inhaled or injected. This highlights just some of the issues that will need to be considered if research into this particular chemical is continued.