on May 8, 2008
Published online before print May 8, 2008, doi: 10.1161/ATVBAHA.108.169078
Submitted on February 14, 2008
Accepted on April 24, 2008
Defective Mer Receptor Tyrosine Kinase Signaling in Bone Marrow Cells Promotes Apoptotic Cell Accumulation and Accelerates Atherosclerosis
Hafid Ait-Oufella ;
From the Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 689 (H.A.-O., V.P., T.S., O.B.-B., K.K., R.M., A.T., Z.M.), Centre de Recherche Cardiovasculaire Lariboisière, Paris, France; Service de Réanimation Médicale (H.A.-O., G.O.), Hôpital Saint-Antoine, Paris, France; Service de Chirurgie Thoracique et Vasculaire (G.L.), Hôpital Bichat, Paris, France; and Philadelphia VA Medical Center (P.L.C.), University of Pennsylvania, Philadelphia.
* To whom correspondence should be addressed. E-mail: mallat{at}larib.inserm.fr.
Objective—To study the role of Mer receptor tyrosine kinase (mertk) in atherosclerosis.
Methods and Results—We irradiated and reconstituted atherosclerosis-susceptible C57Bl/6 low-density lipoprotein receptor–deficient female mice (ldlr-/-) with either a mertk+/+ or mertk-/- (tyrosine kinase-defective mertk) bone marrow. The mice were put on high-fat diet for either 8 or 15 weeks. Mertk deficiency led to increased accumulation of apoptotic cells within the lesions, promoted a proinflammatory immune response, and accelerated lesion development.
Conclusions—Mertk expression by bone marrow–derived cells is required for the disposal of apoptotic cells and controls lesion development and inflammation.
Key words: apoptosis • atherosclerosis • phagocytosis • inflammation