» Articles » PMID: 37459672

Effects of Atorvastatin in Suppressing Pulmonary Vascular Remodeling in Rats with Chronic Obstructive Pulmonary Disease

Overview
Publisher Elsevier
Specialty General Medicine
Date 2023 Jul 17
PMID 37459672
Authors
Affiliations
Soon will be listed here.
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.

References
1.
Barnes P, Celli B . Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009; 33(5):1165-85. DOI: 10.1183/09031936.00128008. View

2.
Putcha N, Drummond M, Wise R, Hansel N . Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management. Semin Respir Crit Care Med. 2015; 36(4):575-91. PMC: 5004772. DOI: 10.1055/s-0035-1556063. View

3.
Young R, Hopkins R, Eaton T . Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2010; 18(114):222-32. DOI: 10.1183/09059180.00005309. View

4.
Hamzeh M, Hosseinimehr S, Khalatbary A, Mohammadi H, Dashti A, Talebpour Amiri F . Atorvastatin mitigates cyclophosphamide-induced hepatotoxicity via suppression of oxidative stress and apoptosis in rat model. Res Pharm Sci. 2018; 13(5):440-449. PMC: 6082033. DOI: 10.4103/1735-5362.236837. View

5.
Barnes P . Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol. 2008; 71:451-64. DOI: 10.1146/annurev.physiol.010908.163257. View