TY - JOUR
T1 - Increase in circulating ACE-positive endothelial microparticles during acute lung injury
AU - Takei, Yusuke
AU - Yamada, Mitsuhiro
AU - Saito, Koji
AU - Kameyama, Yoshinobu
AU - Sugiura, Hisatoshi
AU - Makiguchi, Tomonori
AU - Fujino, Naoya
AU - Koarai, Akira
AU - Toyama, Hiroaki
AU - Saito, Kazutomo
AU - Ejima, Yutaka
AU - Kawazoe, Yu
AU - Kudo, Daisuke
AU - Kushimoto, Shigeki
AU - Yamauchi, Masanori
AU - Ichinose, Masakazu
N1 - Funding Information:
Conflict of interest: Y. Takei has nothing to disclose. M. Yamada reports grants from Japan Society for the Promotion of Science, during the conduct of the study; grants from Novartis, personal fees for lectures from Pfizer, Meiji Seika Pharma and AstraZeneca, outside the submitted work. Koji Saito reports grants from Japan Society for the Promotion of Science, during the conduct of the study. Y. Kameyama has nothing to disclose. H. Sugiura reports grants from Japan Society for the Promotion of Science, outside the submitted work. T. Makiguchi reports grants from Japan Society for the Promotion of Science, outside the submitted work. N. Fujino reports grants from Japan Society for the Promotion of Science, outside the submitted work. A. Koarai reports grants from Japan Society for the Promotion of Science, Novartis and Terumo Foundation for Life Sciences and Arts, outside the submitted work. H. Toyama reports grants from Japan Society for the Promotion of Science, outside the submitted work. Kazutomo Saito reports grants from Japan Society for the Promotion of Science, outside the submitted work. Y. Ejima has nothing to disclose. Y. Kawazoe has nothing to disclose. D. Kudo reports personal fees for lectures from Asahikasei Pharma, Japan Blood Products Organization and Sumitomo Dainippon Pharma, outside the submitted work. S. Kushimoto has nothing to disclose. M. Yamauchi reports grants from Japan Society for the Promotion of Science and Japan Agency for Medical Research and Development, outside the submitted work. M. Ichinose reports personal fees for lectures from Boehringer Ingelheim and AstraZeneca, grants from Astellas, grants from Shionogi, Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Taiho Pharmaceutical Co., AstraZeneca, Fukuda Denshi, Japan Society for the Promotion of Science and Japan Agency for Medical Research and Development, outside the submitted work.
Funding Information:
Acknowledgements: We thank Brent K. Bell (Tohoku University Graduate School of Medicine, Sendai, Japan) for critical reading of the manuscript and language assistance. We acknowledge the support of the Biomedical Research Unit of Tohoku University Hospital. We thank M. Kondo (Tohoku University Graduate School of Medicine, Sendai, Japan) for clerical support.
Funding Information:
We thank Brent K. Bell (Tohoku University Graduate School of Medicine, Sendai, Japan) for critical reading of the manuscript and language assistance. We acknowledge the support of the Biomedical Research Unit of Tohoku University Hospital. We thank M. Kondo (Tohoku University Graduate School of Medicine, Sendai, Japan) for clerical support.
Publisher Copyright:
Copyright © ERS 2019
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Circulating endothelial microparticles (EMPs) are considered to be markers of endothelial injury, and lung microvascular endothelial cells express higher levels of angiotensin-converting enzyme (ACE). The aim of this study is to examine whether the number of ACE+ microvascular EMPs could be a prognostic marker for the development of acute respiratory distress syndrome (ARDS) in septic patients. The numbers of EMPs and ACE+ EMPs in the culture supernatant from human microvascular endothelial cells, as well as in the blood of mouse lung injury models and septic patients (n=82), were examined using flow cytometry. ACE+ EMPs in the culture supernatant from pulmonary microvascular endothelial cells increased after exposure to an inflammatory stimulus. In the mouse lung injury models, the circulating ACE+ EMPs and ACE+ EMP/EMP ratio were higher than in the controls (p<0.001). The ACE+ EMP/EMP ratio was correlated with the wet/dry lung ratio (rs=0.775, p<0.001). The circulating ACE+ EMPs and ACE+ EMP/ EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001). Therefore, circulating ACE+ EMPs may be a prognostic marker for the development of ARDS in the septic patients.
AB - Circulating endothelial microparticles (EMPs) are considered to be markers of endothelial injury, and lung microvascular endothelial cells express higher levels of angiotensin-converting enzyme (ACE). The aim of this study is to examine whether the number of ACE+ microvascular EMPs could be a prognostic marker for the development of acute respiratory distress syndrome (ARDS) in septic patients. The numbers of EMPs and ACE+ EMPs in the culture supernatant from human microvascular endothelial cells, as well as in the blood of mouse lung injury models and septic patients (n=82), were examined using flow cytometry. ACE+ EMPs in the culture supernatant from pulmonary microvascular endothelial cells increased after exposure to an inflammatory stimulus. In the mouse lung injury models, the circulating ACE+ EMPs and ACE+ EMP/EMP ratio were higher than in the controls (p<0.001). The ACE+ EMP/EMP ratio was correlated with the wet/dry lung ratio (rs=0.775, p<0.001). The circulating ACE+ EMPs and ACE+ EMP/ EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001). Therefore, circulating ACE+ EMPs may be a prognostic marker for the development of ARDS in the septic patients.
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U2 - 10.1183/13993003.01188-2018
DO - 10.1183/13993003.01188-2018
M3 - Article
C2 - 31320458
AN - SCOPUS:85073580426
VL - 54
JO - Scandinavian Journal of Respiratory Diseases
JF - Scandinavian Journal of Respiratory Diseases
SN - 0903-1936
IS - 4
M1 - 01188
ER -