Targeting the airway smooth muscle for asthma treatment.
Asthma is a complex respiratory disease whose incidence has increased worldwide in the last decade. Currently there is no cure for asthma. Although bronchodilator and anti-inflammatory medications are effective medicines in some asthmatic patients, it is clear that an unmet therapeutic need persists for a subpopulation of individuals with severe asthma. This chronic lung disease is characterized by airflow limitation, lung inflammation, and remodeling that includes increased airway smooth muscle (ASM) mass. In addition to its contractile properties, the ASM also contributes to the inflammatory process by producing active mediators, which modify the extracellular matrix composition and interact with inflammatory cells. These undesirable functions make interventions aimed at reducing ASM abundance an attractive strategy for novel asthma therapies. The following three mechanisms could limit the accumulation of smooth muscle: decreased cell proliferation, augmented cell apoptosis, and reduced cell migration into the smooth muscle layer. Inhibitors of the mevalonate pathway or statins hold promise for asthma treatment, because they exhibit anti-inflammatory, antimigratory, and antiproliferative effects in preclinical and clinical studies, and they can target the smooth muscle. This review will discuss current knowledge of ASM biology and identify gaps in the field to stimulate future investigations of the cellular mechanisms that control ASM overabundance in asthma. Targeting ASM has the potential to be an innovative venue of treatment for patients with asthma.
Camoretti-Mercado
Blanca
B
Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA. bcamoret@medicine.bsd.uchicago.edu
D000402:Airway Obstruction / Q000503:physiopathology; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D018929:Cell Culture Techniques / Q000379:methods; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology*; D016032:Randomized Controlled Trials as Topic
D018927:Anti-Asthmatic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors