Understanding and avoiding side effects caused by statins

Statin-induced dysfunction of ryanodine receptor channels

Statins are effective cholesterol-lowering drugs that reduce people’s risk of heart attacks and strokes. However, some people taking statins can experience side effects in their muscles. In very rare cases, it can lead to a potentially fatal condition called rhabdomyolysis, where muscle fibres die and release their contents into the bloodstream, causing serious complications. The most commonly used statins, simvastatin and atorvastatin, both switch on a molecule in muscle cells called the ryanodine receptor (RyR1). However, they also block a different subtype of the receptor called RyR2, which is found in the heart. Professor Rebecca Sitsapesan and her team at University of Oxford will investigate exactly how statins differentially affect RyR1 and RyR2 receptors and identify how statins interact with them. They will test several statin drugs to compare how they bind to different types of RyR receptor and how each statin affects receptor function. They also have access to muscle cells taken from people with a RyR1 mutation, or fault, that is linked to exercise-induced rhabdomyolysis. Using these mutated cells, they will test whether statins cause more pronounced side effects on the faulty RyR1. This could help to identify statins users who are most at risk of serious muscular side effects. This work will help to identify statin molecules that can lower blood cholesterol levels without affecting RyR, thus reducing the likelihood of side-effects.