Reference - Detail
|Author||Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K.|
|Title||Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin.|
|Journal||Pulm Pharmacol Ther|
BACKGROUND:Statin use in individuals with chronic obstructive pulmonary disease (COPD) with coexisting cardiovascular disease is associated with a reduced risk of exacerbations. The mechanisms by which statin plays a role in the pathophysiology of COPD have not been defined. To explore the mechanisms involved, we investigated the effect of statin on endothelial cell function, especially endothelial cell tight junctions.
METHOD:We primarily assessed whether pitavastatin could help mitigate the development of emphysema induced by continuous cigarette smoking (CS) exposure. We also investigated the activation of liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling, which plays a role in maintaining endothelial functions, important tight junction proteins, zonula occludens (ZO)-1 and claudin-5 expression, and lung microvascular endothelial cell permeability.
RESULTS:We found that pitavastatin prevented the CS-induced decrease in angiomotin-like protein 1 (AmotL1)-positive vessels via the activation of LKB1/AMPK signaling and IFN-γ-induced hyperpermeability of cultured human lung microvascular endothelial cells by maintaining the levels of AmotL1, ZO-1, and claudin-5 expression at the tight junctions.
CONCLUSION:Our results indicate that the maintenance of lung microvascular endothelial cells by pitavastatin prevents tight junction protein dysfunctions induced by CS. These findings may ultimately lead to new and novel therapeutic targets for patients with COPD.
|MeSH||Angiopoietin-Like Protein 1 Animals Capillary Permeability / drug effects Disease Models, Animal Endothelial Cells / drug effects* Endothelial Cells / metabolism Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Lung / cytology Lung / drug effects Membrane Proteins / metabolism Mice Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / genetics Pulmonary Emphysema / etiology Pulmonary Emphysema / prevention & control* Quinolines / pharmacology* Smoking / adverse effects Tight Junction Proteins / drug effects* Tight Junction Proteins / metabolism Tight Junctions / drug effects Tight Junctions / metabolism|
|WOS Category||PHARMACOLOGY & PHARMACY RESPIRATORY SYSTEM|