Statin drugs and lipid modulation: Mechanistic basis considering lipid rafts, kinase signaling, myopathy, and cancer
Suditi Karthikeyan, Poornima Somasundaram, Isaac Karimi, Francisco Alejandro Lagunas‐Rangel, Ahmed M. Alsehli, Robert Fredriksson, Jörgen Jönsson, Helgi B. Schiöth
Abstract
Statins are drugs that have been widely used to decrease the levels of cholesterol and are usually well tolerated. Increasing evidence suggests that these lipid-lowering drugs can impact the structural and functional integrity of lipid rafts, which are regulators for cellular signaling, protein trafficking, and membrane dynamics. This review discusses the dual actions of statins, encompassing both enzymatic inhibition and direct biophysical interactions with lipid membranes. The hydrophobicity of statins may drive the selective disruption of the raft components, potentially influencing major pathways related to kinase signaling, mitochondrial dynamics, and membrane protein localization. Such disruptions can have adverse impacts, such as statin-associated myopathy, in addition to therapeutic advantages, such as anti-inflammatory and anticancer effects. The role of caveolins in stabilizing lipid rafts and their association with muscle diseases are also discussed in this review. Besides this, the article explores the significance of raft modulation in many biological contexts, such as viral entry, autoimmune regulation, and antimicrobial resistance. By incorporating recent advances, this review highlights the importance of considering the action of statins from the perspective of membrane biology, paving the way for more targeted and safer therapeutic approaches.