Microparticles from apoptotic vascular smooth muscle cells induce endothelial dysfunction, a phenomenon prevented by β3-integrin antagonists

Sanah Essayagh; Anne-Cecile Brisset; Anne-Dominique Terrisse; Dominique Dupouy; Lise Tellier; Chantal Navarro; Jean-François Arnal; Piérre Siè

doi:10.1160/TH04-12-0786

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 94(04): 853-858
DOI: 10.1160/TH04-12-0786

Endothelium and Vascular Development

Schattauer GmbH

Microparticles from apoptotic vascular smooth muscle cells induce endothelial dysfunction, a phenomenon prevented by β3-integrin antagonists

Sanah Essayagh^*

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

,

Anne-Cecile Brisset^*

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

,

Anne-Dominique Terrisse

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

,

Dominique Dupouy

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

,

Lise Tellier

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

,

Chantal Navarro

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

,

Jean-François Arnal

²U 589 INSERM, Institut Louis Bugnard, Hôpital Rangueil, Toulouse, France

,

Piérre Siè

¹EA 2049, Laboratoire de Recherche sur la Thrombose, Université Paul Sabatier, Toulouse, France

› Institutsangaben

Abstract

Summary

Fragile atherosclerotic plaques are rich in apoptotic smooth muscle cells (SMCs) and macrophages, generating microparticules (MPs) which accumulate locally and may be released in blood in case of mechanical or spontaneous plaque disruption. Besides being highly procoagulant, this material may interact with downstream endothelium. Using a model of mouse aorta vaso-reactivity, we have investigated the effects of apoptotic MPs preparedin vitro from Fas-ligand sensitive SMCs. Short-term preincubation of aorta rings with the MPs dose-dependently reduced the vasodilatory response to acetylcholine dependent on the endothelium. This effect was prevented by the addition of abxicimab or eptifibatide, indicating a role for a β3 integrin in thisprocess. We further investigated its mechanism using cultured endothelial cells. The MPs were found to bind to the cells and to inhibit the production and the release of nitric oxide (NO) in response to bradykinin. This phenomenom was redox sensitive, independent of the generation of activated coagulation proteases, and was abrogated when the MPs were pretreated by trypsin. The metabolic effects of MPs were prevented by the addition of eptifibatide. Taken together, these results suggest a potential, platelet-independent, mechanism for the improvement of microvascular perfusion observed with β3-integrin antagonists.

Keywords

Microparticles - nitric oxide - endothelium - vasorelaxation - β3-integrin antagonists

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Referenzen

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