Alteration in angiotensin-converting enzyme 2 by PM1 during the development of emphysema in rats

Hsiao-Chi Chuang; Yi-Ying Chen; Ta-Chih Hsiao; Hsiu-Chu Chou; Han-Pin Kuo; Po-Hao Feng; Shu-Chuan Ho; Jen-Kun Chen; Kai-Jen Chuang; Kang-Yun Lee

doi:10.1183/23120541.00174-2020

Alteration in angiotensin-converting enzyme 2 by PM₁ during the development of emphysema in rats

ERJ Open Res. 2020 Oct 5;6(4):00174-2020. doi: 10.1183/23120541.00174-2020. eCollection 2020 Oct.

Authors

Hsiao-Chi Chuang^{1

2

3}, Yi-Ying Chen¹, Ta-Chih Hsiao⁴, Hsiu-Chu Chou⁵, Han-Pin Kuo⁶, Po-Hao Feng^{3

6}, Shu-Chuan Ho¹, Jen-Kun Chen⁷, Kai-Jen Chuang^{8

9}, Kang-Yun Lee^{3

6}

Affiliations

¹ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
³ Division of Pulmonary Medicine, Dept of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁴ Graduate Institute of Environmental Engineering, National Taiwan University, Taipei, Taiwan.
⁵ Dept of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁶ Division of Pulmonary Medicine, Dept of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
⁸ School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
⁹ Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

Introduction: Angiotensin-converting enzyme 2 (ACE2) provides an adhesion site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with COPD could have severe outcomes after SARS-CoV-2 infection. The objective of this study was to investigate ACE2 regulation by air pollution during the development of COPD.

Methods: Sprague Dawley rats were exposed to unconcentrated traffic-related air pollution for 3 and 6 months. We examined lung injury markers, oxidative stress, inflammation, emphysema, ACE2 and angiotensin II receptor type 1 (AT1) and 2 (AT2) in the lungs after exposure.

Results: Lung injury occurred due to an increase in permeability and lactate dehydrogenase cytotoxicity was observed after 6 months of exposure to fine particulate matter of <1 μm in aerodynamic diameter (PM₁). An α₁-antitrypsin deficiency and neutrophil elastase production with emphysema development were observed after 6 months of PM₁ exposure. 8-isoprostane and interleukin-6 were increased after 3 and 6 months of PM₁ exposure. Caspase-3 was increased after exposure to PM₁ for 6 months. Upregulation of ACE2 was found after 3 months of PM₁ exposure; however, ACE2 had decreased by 6 months of PM₁ exposure. AT1 and AT2 had significantly decreased after exposure to PM₁ for 6 months. Furthermore, smooth muscle hypertrophy had occurred after 6 months of PM₁ exposure.

Conclusions: In conclusion, short-term exposure to PM₁ increased the ACE2 overexpression in lungs. Long-term exposure to PM₁ decreased the ACE2 overexpression in emphysema. Air pollution may be a risk for SARS-CoV-2 adhesion during the development of COPD.