Validation of the pitavastatin-induced angiomotin-like protein 1 that controls tight junction stability of lung microvascular endothelial cells via LKB1/AMPK activation

Abstract

Background: Angiogenesis has been suggested to be one of the critical factors in the pathogenesis of pulmonary emphysema. We have demonstrated that angiomotin-like protein 1 (AmotL1) controls tight junction stability of human lung microvascular endothelial cells (HLMVECs). Subsequently, AmotL1-positive vessels have shown to be decreased in emphysema lungs when compared to normal lungs.

Objectives: We examined a hypothesis that states that statin regulates AmotL1.

Methods: A murine model with emphysema compared the differences of air space enlargement and AmotL1 positive vessels in lungs with and without pitavastatin pretreatment. We determined that the pitavastatin regulates the AmotL1 expression via the Liver Kinase B1 (LKB1)/ AMP-activated protein kinase (AMPK) pathway that is a sensor of cellular energy levels in cultured HLMVECs.

Results: We found that pitavastatin prevented a decreasing of AmotL1 positive endothelial cells and air space enlargement in the emphysema mouse model via LKB1/AMPK activation in HLMVECs.

Conclusions: Thus, pitavastatin enhances the LKB1/AMPK pathway to increase the maintenance of pulmonary vessels, which is expected to affect the risk of exacerbations of emphysema.