Open Access

Amr Mohamaden Abdelkader Mohamed

• Statins are a group of hypolipidemic drugs that act by competitive inhibition of the HMGR enzyme. They are generally considered effective and safe but claimed to have side effects on skeletal muscles. A molecular side effect of statins is the block of terpene biosynthesis and hence of dolichol involved in N-glycosylation and O-mannosylation of proteins. Defects in O-mannosylation lead to α-dystroglycan (α-DG) hypoglycosylation and a series of hereditary dystroglycanopathies. The current project aims to get insight into molecular pathomechanisms induced by statins in mammalian muscle cells and to unravel a potential link between these effects and statin-induced decreases of α-DG O-mannosylation. The study was based on mass spectrometric proteomics supported by western blot analysis to reveal Rosuvastatin effects on cellular pathways under high (micromolar) or low (nanomolar) conditions. Differential proteomics revealed higher statin effects on muscle cell function in micromolar than nanomolar concentration, which is reached in the patient’s plasma. We demonstrated distinct and partially overlapping patterns of fold-changed proteins under high and low statin conditions. Gene ontology term enrichment (GOTE) analyses of fold-changed proteins revealed cellular pathways related to muscle function and development are affected, even under low statin conditions, typically reached in the patient’s plasma during prophylactic medication.