Effects of atorvastatin in suppressing pulmonary vascular remodeling in rats with chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling. METHODS: Eighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR). RESULTS: Compared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p < 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p < 0.05). CONCLUSION: The present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.

Hypoxia promotes epithelial-mesenchymal transition in lung cancer cells via regulating the NRF2/miR­27a/BUB1 pathway.

PURPOSE: Lung cancer (LC) is the most common malignancy in the world. It is well that hypoxia is common in lung cancer, which contributes to lung cancer progression and metastasis [1]. miRNA-27a as a repressor factor is a lowly expression within non-small cell lung cancer (NSCLC). However, the molecular mechanism between miR-27a and hypoxia in lung cancer progression remains poorly understood. This study aims to explore hypoxia promotes epithelial-mesenchymal transition in lung cancer cells via regulating the NRF2/miR­27a/BUB1 pathway. METHODS: We detect the expression of miR-27a after exposure to hypoxia conditions in lung cancer cells via qPCR. Using MTT assay and colony assay to assess the ability of proliferation in lung cancer cells under hypoxia or transfect miR-27a mimics. The capability of migration and invasion was evaluated by wound healing assay and Boyden-chamber assay. The mRNA and protein expression of EMT markers was respectively detected by qPCR and western blot. We detected NRF2 occupancy at the miR-27a promoter by ChIP-Seq analysis. Meanwhile, the luciferase assay verified BUB1 as a direct target of miR-27a. RESULTS: We found hypoxia promotes lung cancer cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT) process by inhibiting the miR-27a expression. miR-27a mimics significantly reduced the promotion effect of hypoxia on the invasion and proliferation of lung cancer cells. NRF2 as regulating the oxidation/anti-oxidation factor was activated under hypoxia conditions. The activation of NRF2 repressed miR-27a expression. On the contrary, the inhibitory effect of hypoxia on miR-27a was reversed when the NFE2L2 gene was silenced. Ectopic expression of NRF2 inhibited miR-27a expression under normoxia. We further validated BUB1 as a direct target of the miR-27a by luciferase assay. CONCLUSION: Hypoxia promotes invasion and epithelial-mesenchymal transition of Lung cancer cells by regulating the NRF2/miR-27a/BUB1 axis.

Effects of atorvastatin in suppressing pulmonary vascular remodeling in rats with chronic obstructive pulmonary disease

Abstract Objective To investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling. Methods Eighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR). Results Compared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p< 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p< 0.05). Conclusion The present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.