Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin

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• 作者：Rioto Suzuki^a ; ^{m38_riotos@yahoo.co.jp" class="auth_mail" title="E-mail the corresponding author} ; Yutaka Nakamura^a ; ^{ICB75097@nifty.com" class="auth_mail" title="E-mail the corresponding author} ; Shinji Chiba^a ; ^{shinji6311chiba@yahoo.co.jp" class="auth_mail" title="E-mail the corresponding author} ; Tomoki Mizuno^a ; ^{tmizuno1004@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Kazuyuki Abe^a ; ^{anything3137@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Yosuke Horii^a ; ^{m06092yh@jichi.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Hiromi Nagashima^a ; ^{all-checker1983@m7.dion.ne.jp" class="auth_mail" title="E-mail the corresponding author} ; Tatsuo Tanita^b ; ^{ttanita@iwate-med.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Kohei Yamauchi^a ; ^{kyamauch@iwate-med.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：COPD ; Statin ; Exacerbation ; Tight junction ; AmotL1
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：38
• 期：Complete
• 页码：27-35
• 全文大小：1475 K

文摘

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.