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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00941

Cigarette smoke reduces fatty acid catabolism, leading to apoptosis in lung endothelial cells: implication for pathogenesis of COPD

 Jiannan Gong1,  Hui Zhao1, Tanzhen Liu1, Lifang Li1, Erjing Cheng1, Shuyin Zhi1, Lufei Kong1, Hongwei Yao1* and Jianqiang Li1*
  • 1Department of Respiratory and Critical Care Medicine, Second Hospital of Shanxi Medical University, China

Endothelial cell (EC) apoptosis contributes to cigarette smoke (CS)-induced pulmonary emphysema. Metabolism of glucose, glutamine and fatty acid is dysregulated in patients with chronic obstructive pulmonary disease (COPD). Whether CS causes metabolic dysregulation in ECs, leading to development of COPD remains elusive. We hypothesized that CS alters metabolism, resulting in apoptosis in lung ECs. To test this hypothesis, we treated primary mouse pulmonary microvascular ECs (PMVECs) with CS extract (CSE), and employed PMVECs from healthy subjects and COPD patients. We found that mitochondrial respiration was reduced in CSE-treated PMVECs, and in PMVECs from COPD patients. Specifically, oxidation of fatty acids (FAO) was reduced in these cells, which linked to reduced carnitine palmitoyltransferase 1a (Cpt1a), an essential enzyme for carnitine shuttle. CSE-induced apoptosis was further increased when cells were treated with a specific Cpt1 inhibitor etomoxir or transfected with Cpt1a siRNA. L-carnitine treatment augmented FAO, but attenuated CSE-induced apoptosis by upregulating Cpt1a. CSE treatment increased palmitate-derived ceramide synthesis, which was reduced by L-carnitine. Although CSE treatment increased glycolysis, inhibiting glycolysis with 2-Deoxy-D-glucose had no effects on CSE-mediated apoptosis in lung ECs. Conclusively, FAO reduction increases ceramide and apoptosis in lung ECs treated with CSE, which may contribute to the pathogenesis of COPD/emphysema.

Keywords: chronic obstructive pulmonary disease, Endothelial Cells, Metabolism, ceramide, Apoptosis

Received: 30 Apr 2019; Accepted: 24 Jul 2019.

Edited by:

Paolo Montuschi, Catholic University of the Sacred Heart, Italy

Reviewed by:

Oren Rom, Michigan Medicine, University of Michigan, United States
Dolors Serra, University of Barcelona, Spain
Weiliang Qiu, Sanofi Genzyme, United States  

Copyright: © 2019 Gong, Zhao, Liu, Li, Cheng, Zhi, Kong, Yao and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Hongwei Yao, Second Hospital of Shanxi Medical University, Department of Respiratory and Critical Care Medicine, Taiyuan, China,
Dr. Jianqiang Li, Second Hospital of Shanxi Medical University, Department of Respiratory and Critical Care Medicine, Taiyuan, China,