Angiotensin-converting enzyme-2 overexpression attenuates inflammation in rat model of chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the anti-inflammatory effects of angiotensin-converting enzyme 2 (ACE2) overexpression on rat model of chronic obstructive pulmonary disease (COPD), and explore underlying mechanism.
METHODS: The rat COPD model was established by cigarette smoking using a total body exposure method. A total of 64 male Wistar rats were randomly divided into four groups: normal, COPD, Ad-ACE2 and Ad-EGFP groups. The COPD model rats (including COPD, Ad-ACE2 and Ad-EGFP groups) received an intratracheal injection of normal saline, Ad-ACE2 and Ad-EGFP, respectively. The normal group underwent the same procedure but received an intratracheal injection of normal saline only. Pulmonary function tests, lung histopathology analysis, malondialdehyde (MDA) and reactive oxygen species (ROS) level, ACE2 mRNA and protein expression level, inflammatory cytokines and related signaling pathway proteins were measured.
RESULTS: COPD rats showed impairment of lung function as evidenced by decreased ratio of forced expiratory volume at 0.3 s and forced vital capacity (FEV0.3/FVC) and dynamic lung compliance (Cldyn), increased resistance inspiration (Ri) and resistance expiration (Re) as compared with the normal group, accompanying with reduced ACE2 mRNA expression, elevated ROS and MDA, elevated inflammatory cytokines levels (tumor necrosis factor α, TNF-α; interleukin-8, IL-8; IL-2 and IL-1β) and activation of nuclear factor-κB (NF-κB) and p38 MAPK (mitogen activated protein kinases) pathway in lung tissues. ACE2 overexpression through Ad-ACE2 infusion significantly attenuated the inflammatory response in lung tissues of COPD model rats.
CONCLUSION: ACE2 could attenuate COPD inflammatory process induced by cigarette smoke through reduction of oxidative stress and inhibition of NF-κB and p38 MAPK pathway activation.