Do cholesterol drugs reduce clot risk?

“Drugs which can regulate levels of cholesterol in the blood may also reduce the risk of dangerous clots,” reported BBC News. Its said a study which looked at whether proteins involved in regulating cholesterol, called Liver X receptors (LXRs), might be involved in the activity of platelets, the cells that play a key role in blood clotting. Dangerous blood clots in blood vessels, known as thrombosis, can trigger heart attacks and strokes.

Researchers found that experimental drugs that target LXRs also appeared to inhibit platelet activity in mice, reducing blood clotting by 40%. They say these findings suggest that drugs which lower cholesterol by targeting LXRs could also prevent and treat thrombosis.

This is intricate research, and the findings are noteworthy. However, this is also an early stage laboratory study, testing the effects of experimental drugs on mice that were prone to developing thrombosis. Also, the study only looked at how blood clots reacted to experimental drugs known to affect cholesterol metabolism in mice, rather than drugs that are actually used to lower cholesterol in humans. These experimental drugs themselves are not yet available for human use. Far more research is required, including trials in humans.

Where did the story come from?

The study was carried out by researchers from the University Of Reading, and it was funded by the British Heart Foundation and Heart Research UK. The study was published in the peer-reviewed journal Blood .

The study was reported accurately by the BBC and The Daily Telegraph , although neither of them reported that this was early stage research.

What kind of research was this?

The laboratory study investigated the potential role of a type of protein (called Liver X receptors [LXRs]) in platelets (cell-like particles in the blood that regulate clotting activity). The protein is known to be involved in regulating cholesterol metabolism.

The researchers say that previous research has found that synthetic LXR “ligands” (molecules that bind to LXRs and affect their function) can reduce atherosclerosis (hardening of the arteries) independently of their effects on cholesterol.

In this study, they tested whether LXR ligands could affect platelets and reduce the risk of blood clots in mice. To begin with, the researchers analysed human blood to see whether LXRs are present in platelets. They then experimented on mice to assess whether drugs that target LXRs have a beneficial effect on clotting.

What did the research involve?

The research had two parts. To assess whether human platelets contain LXRs, the researchers first obtained human blood from healthy volunteers. The blood was specially prepared in the laboratory so that scientists could measure LXRs within the platelets and look at their activity.

The researchers collected 50ml of blood in a syringe containing 3ml of anti-coagulant. Platelets in the blood were collected and ‘washed’ by spinning the blood. The platelets were then re-suspended in a sugary solution and rested for half an hour at 30ºC before the experiments began.

The researchers measured levels of LXR within the platelets by taking the washed platelets and incubating them with labelled antibodies to LXRβ. The labelled antibodies ‘stuck’ to the platelets, making them identifiable and capable of being measured. The researchers then measured the amount of labelled antibody using specific detection processes.

In the second part, mice that had been prepared to develop thrombi (blood clots) were tested to see whether synthetic LXR ligands called GW3965, originally developed as experimental drugs to control cholesterol, could reduce the size or stability of the clots.

What were the basic results?

In summary, the researchers found that the protein LXR is present in human platelets. When tested in mice with blood clots, GW3965 had anti-clotting effects, reducing the size and stability of clots by 40%.

How did the researchers interpret the results?

The researchers say they have found that a molecule that binds to LXRs called GW3965, already known to help regulate cholesterol, also has an anti-clotting effect. They say this finding could lead to the development of new drugs to prevent and treat thrombosis.

Conclusion

This study found that chemicals targeting proteins called LXRs can reduce blood clot formation in mice. The researchers suggest that LXRs, already known to help regulate cholesterol, are also involved in regulating the activity of platelets, the cells involved in blood clotting. Therefore, it is possible that new drugs that target LXR to control cholesterol could also reduce the risk of thrombosis.

The finding of this early stage research is noteworthy, but it is important to bear in mind that this laboratory study tested the effects of experimental drugs on mice that had been made to develop thrombosis. Also, the study only looked at how blood clots reacted to experimental drugs, rather than drugs that are actually used to lower cholesterol. These experimental drugs themselves are not yet available for human use. Far more research is required. If safety tests for the experimental drugs are passed, then trials in humans may be possible.