The movement of blood through arteries may affect the action of the cholesterol-lowering statin drugs, say scientists.
Statins reduce levels of harmful low density lipoprotein cholesterol among patients at risk of cardiovascular disease. The drugs are also thought to produce antioxidants in the arteries by boosting levels of an enzyme called heme oxygenase-1.
To investigate this effect, Dr Justin Mason and colleagues at Imperial College London, UK, examined the action of statins in different parts of the circulation. They measured the amount of the enzyme in endothelial cells that line arteries.
Results showed that the increase in the enzyme caused by the drug was significantly higher in cells exposed to fast and regular blood flow, compared to those cells exposed to sluggish or disrupted blood flow.
This is the first evidence that biomechanical forces may affect a drug’s action, they state in the Journal of Biological Chemistry. The discovery may highlight new targets to improve artery health throughout the body, they add.
Dr Mason said: "Arteries don’t clog up in a uniform way. Bends and branches of blood vessels – where blood flow is disrupted and can be sluggish – are much more prone to fatty plaques building-up and blocking the artery.
"What we’ve shown is that those regions of the arteries most likely to become diseased are the same regions that may not be benefiting maximally from statin treatment – a double whammy.
"We now hope to use these findings to identify a way to get the most out of statins, or to find other ways to switch on protective mechanisms in vulnerable areas of arteries."
Ali, F. et al. Induction of the cytoprotective enzyme heme oxygenase-1 by statins is enhanced in vascular endothelium exposed to laminar shear stress and impaired by disturbed flow. The Journal of Biological Chemistry, Vol. 284, July 2009, pp. 18882-92.
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