Significance of neutrophil microparticles in ischaemia-reperfusion: Pro-inflammatory effectors of endothelial senescence and vascular dysfunction.

Journal of Cellular and Molecular Medicine
Ali El HabhabFlorence Toti

Abstract

Endothelial senescence is an emerging cause of vascular dysfunction. Because microparticles are effectors of endothelial inflammation and vascular injury after ischaemia-reperfusion, we examined leucocyte-derived microparticles of spleen origin as possible contributors. Microparticles were generated from primary rat splenocytes by either lipopolysaccharide or phorbol-myristate-acetate/calcium ionophore, under conditions mimicking innate and adaptive immune responses. Incubation of primary porcine coronary endothelial cells with either type of microparticles, but not with those from unstimulated splenocytes, leads to a similar threefold raise in senescence-associated β-galactosidase activity within 48 hours, indicating accelerated senescence, to endothelial oxidative stress, and a fivefold and threefold increase in p21 and p16 senescence markers after 24 hours. After 12-hour incubation, the endothelial-dependent relaxation of coronary artery rings was reduced by 50%, at distinct optimal microparticle concentration. In vitro, microparticles were pro-thrombotic by up-regulating the local angiotensin system, by prompting tissue factor activity and a secondary generation of pro-coagulant endothelial microparticles. They initiated an...Continue Reading

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Citations

May 4, 2021·Transplantation Proceedings·Mohamad KassemFlorence Toti
Oct 22, 2021·Journal of Thrombosis and Haemostasis : JTH·Antoine CaillonGilles Kauffenstein

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Methods Mentioned

BETA
flow cytometry
PMA
glycosylation
fluorescence microscopy

Software Mentioned

GraphPad Prism5
Izon control suite
qNano

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