Statin drugs, metabolic pathways, and asthma: A therapeutic opportunity needing further research

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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 posses 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.

Original languageEnglish (US)
Pages (from-to)40-44
Number of pages5
JournalDrug Metabolism Letters
Volume5
Issue number1
DOIs
StatePublished - 2011

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Metabolic Networks and Pathways
Asthma
Mevalonic Acid
Research
Pharmaceutical Preparations
Cholesterol
Membrane Microdomains
Therapeutics
Pulmonary diseases
Investigational Therapies
Sphingolipids
Therapeutic Uses
Lung Diseases
Action Potentials
Disease Progression
Pneumonia
Patient Care
Anti-Inflammatory Agents
Cardiovascular Diseases

Keywords

  • Anti-inflammatory
  • Asthma
  • Eotaxin
  • HMG-CoA reductase
  • Immunomodulatory
  • Lipid
  • Metabolic
  • Mevalonate
  • Novel therapy
  • Obese asthmatic
  • Statins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical
  • Pharmacology (medical)
  • Pharmaceutical Science

Cite this

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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 posses 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.",
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