Structural and functional characterization of endothelial microparticles released by cigarette smoke

Karina A. Serban, Samin Rezania, Daniela Petrusca, Christophe Poirier, Danting Cao, Matthew J. Justice, Milan Patel, Irina Tsvetkova, Krzysztof Kamocki, Andrew Mikosz, Kelly S. Schweitzer, Sean Jacobson, Angelo Cardoso, Nadia Carlesso, Walter C. Hubbard, Katerina Kechris, Bogdan Dragnea, Evgeny V. Berdyshev, Jeanette McClintock, Irina Petrache

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown. We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS. CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells. CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium. CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice. The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis. Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages. These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers.

Original languageEnglish (US)
Article number31596
JournalScientific Reports
Volume6
DOIs
StatePublished - Aug 17 2016

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Smoke
Tobacco Products
Sphingomyelin Phosphodiesterase
Ceramides
MicroRNAs
Chronic Obstructive Pulmonary Disease
Macrophages
Exosomes
Acids
Enzymes
Endothelium
Endothelial Cells
Biomarkers
Inflammation
Lung
Wounds and Injuries

ASJC Scopus subject areas

  • General

Cite this

Structural and functional characterization of endothelial microparticles released by cigarette smoke. / Serban, Karina A.; Rezania, Samin; Petrusca, Daniela; Poirier, Christophe; Cao, Danting; Justice, Matthew J.; Patel, Milan; Tsvetkova, Irina; Kamocki, Krzysztof; Mikosz, Andrew; Schweitzer, Kelly S.; Jacobson, Sean; Cardoso, Angelo; Carlesso, Nadia; Hubbard, Walter C.; Kechris, Katerina; Dragnea, Bogdan; Berdyshev, Evgeny V.; McClintock, Jeanette; Petrache, Irina.

In: Scientific Reports, Vol. 6, 31596, 17.08.2016.

Research output: Contribution to journalArticle

Serban, KA, Rezania, S, Petrusca, D, Poirier, C, Cao, D, Justice, MJ, Patel, M, Tsvetkova, I, Kamocki, K, Mikosz, A, Schweitzer, KS, Jacobson, S, Cardoso, A, Carlesso, N, Hubbard, WC, Kechris, K, Dragnea, B, Berdyshev, EV, McClintock, J & Petrache, I 2016, 'Structural and functional characterization of endothelial microparticles released by cigarette smoke', Scientific Reports, vol. 6, 31596. https://doi.org/10.1038/srep31596
Serban, Karina A. ; Rezania, Samin ; Petrusca, Daniela ; Poirier, Christophe ; Cao, Danting ; Justice, Matthew J. ; Patel, Milan ; Tsvetkova, Irina ; Kamocki, Krzysztof ; Mikosz, Andrew ; Schweitzer, Kelly S. ; Jacobson, Sean ; Cardoso, Angelo ; Carlesso, Nadia ; Hubbard, Walter C. ; Kechris, Katerina ; Dragnea, Bogdan ; Berdyshev, Evgeny V. ; McClintock, Jeanette ; Petrache, Irina. / Structural and functional characterization of endothelial microparticles released by cigarette smoke. In: Scientific Reports. 2016 ; Vol. 6.
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