Abstract 9738: Endothelial Microparticles Reduce Icam-1 Expression in a Microrna-222-Dependent Mechanism
Introduction: Endothelial microparticles (EMP) are released from activated or apoptotic endothelial cells (ECs) and can be taken up by adjacent endothelial cells, but their effect on vascular inflammation after engulfment is largely unknown.
Hypothesis: EMP influence endothelial target cell inflammation.
Methods and Results: In vitro, EMP treatment significantly reduced TNF-α-induced endothelial ICAM-1 expression on mRNA and protein level, whereas there was no effect on VCAM-1 expression. Reduced ICAM-1 expression after EMP treatment resulted in diminished monocyte adhesion in vitro. In vivo, systemic treatment of ApoE-/- mice with EMP significantly reduced murine endothelial ICAM-1 expression and infiltration of macrophages into atherosclerotic plaques. In order to explore the underlying mechanisms, Taqman microRNA-array was performed and microRNA (miR)-222 was identified as the strongest regulated miR between EMP and endothelial cells. Following experiments demonstrated that miR-222 was transported into recipient endothelial cells by EMP and functionally regulated expression of its target protein ICAM-1. Interestingly, after simulating diabetic conditions, EMP derived from glucose-treated ECs contained significantly lower amounts of miR-222 and showed reduced anti-inflammatory capacity in vitro and in vivo.
Conclusions: Endothelial microparticles promote anti-inflammatory effects in vitro and in vivo by reducing endothelial ICAM-1 expression via the transfer of functional microRNA-222 into recipient cells. In pathological hyperglycaemic conditions, EMP-mediated miR-222-dependent anti-inflammatory effects are reduced.
Author Disclosures: F. Jansen: None. K. Baumann: None. G. Nickenig: None. N. Werner: None.
- © 2014 by American Heart Association, Inc.