title: Statin drugs, metabolic pathways, and asthma: a therapeutic opportunity needing further research.
abstract: The chance discovery of hydroxymethylglutaryl (HMG)-CoA reductase inhibitors has revolutionized the care of patients with cardiovascular disease. The unexpected finding that these cholesterol-lowering drugs (or 'statins') also possess pleiotropic immunomodulatory properties, has opened a new area of research which investigates the anti-inflammatory and anti-proliferative properties of statins. In this brief commentary, we discuss the potential application of these drugs in asthma, where metabolic pathways pertinent to lung inflammation, in addition to the mevalonate cascade, may be targeted. We review mechanisms of action, discuss the potential therapeutic use of statins in asthma, share some preliminary data from our laboratory, discuss results from recent clinical trials in asthma, and propose a new target asthma subpopulation that could potentially benefit. We conclude our essay by highlighting the mevalonate-dependent and -independent pathways that may be modulated by statins, including the emerging area of cholesterol, sphingolipid, and lipid raft biology in lung disease. In this is an opportunity to develop new treatments for asthma, where innovative therapies are urgently needed to prevent acute exacerbations and alter disease progression.
authors.affiliation: University of California, Davis, Department of Internal Medicine, Division of Pulmonary, Critical Care, and SleepMedicine, Davis, CA 95616, USA.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Zeki
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
authors.forename: Tzipora
authors.initials: T
authors.lastname: Goldkorn
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D055808:Drug Discovery; D019317:Evidence-Based Medicine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008798:Mevalonic Acid