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Increase in circulating ACE-positive endothelial microparticles during acute lung injury
Selasa, 27 Ags 2019 10:01:02

Yusuke TakeiMitsuhiro YamadaKoji SaitoYoshinobu KameyamaHisatoshi SugiuraTomonori MakiguchiNaoya FujinoAkira KoaraiHiroaki ToyamaKazutomo SaitoYutaka EjimaYu KawazoeDaisuke KudoShigeki KushimotoMasanori YamauchiMasakazu Ichinose

European Respiratory Journal 2019; DOI: 10.1183/13993003.01188-2018

Abstract

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 by 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-to-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).

Circulating ACE+ EMPs may therefore be a prognostic marker for the development of ARDS in the septic patients.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Takei has nothing to disclose.

Conflict of interest: Dr. Yamada reports grants from Japan Society for the Promotion of Science, during the conduct of the study; grants from Novartis, personal fees from Pfizer, personal fees from Meiji Seika Pharma, personal fees from AstraZeneca, outside the submitted work.

Conflict of interest: Dr. Koji Saito reports grants from Japan Society for the Promotion of Science, outside the submitted work.

Conflict of interest: Dr. Sugiura reports grants from Japan Society for the Promotion of Science, outside the submitted work.

Conflict of interest: Dr. Makiguchi reports grants from Japan Society for the Promotion of Science, outside the submitted work.

Conflict of interest: Dr. Fujino reports grants from Japan Society for the Promotion of Science, outside the submitted work.

Conflict of interest: Dr. Koarai reports grants from Japan Society for the Promotion of Science, grants from Novartis, grants from Terumo Foundation for Life Sciences and Arts, outside the submitted work.

Conflict of interest: Dr. Toyama reports grants from Japan Society for the Promotion of Science, outside the submitted work.

Conflict of interest: Kazutomo Saito Dr. Saito reports grants from Japan Society for the Promotion of Science, outside the submitted work

Conflict of interest: Dr. Ejima has nothing to disclose.

Conflict of interest: Dr. Kawazoe has nothing to disclose.

Conflict of interest: Dr. Kudo reports personal fees for lectures from Asahikasei pharma, personal fees for lectures from Japan Blood Products Organization, personal fees for lectures from Sumitomo Dainippon Pharma, outside the submitted work.

Conflict of interest: Dr. Kushimoto has nothing to disclose.

Conflict of interest: Masanori Yamauchi

Conflict of interest: Dr. Ichinose reports personal fees from Boehringer Ingelheim (fees for lectures), personal fees from AstraZeneca (fees for lectures), grants from Astellas, grants from SHIONOGI, grants from Pfizer, grants from DAIICHI SANKYO, grants from Boehringer Ingelheim, grants from TAIHO Phamaceutical Co, grants from AstraZeneca, grants from FUKUDA DENSHI, grants from Japan Society for the Promotion of Science, grants from Japan Agency for Medical Research and Development, outside the submitted work.

Conflict of interest: Dr. Kameyama has nothing to disclose.