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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1429.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Defective Mer Receptor Tyrosine Kinase Signaling in Bone Marrow Cells Promotes Apoptotic Cell Accumulation and Accelerates Atherosclerosis

Hafid Ait-Oufella; Vahid Pouresmail; Tabassome Simon; Olivier Blanc-Brude; Kiyoka Kinugawa; Régine Merval; Georges Offenstadt; Guy Lesèche; Philip L. Cohen; Alain Tedgui; Ziad Mallat

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.

Correspondence to Ziad Mallat, MD, PhD, Inserm U689, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France. 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.

To study the role of mertk in atherosclerosis, we irradiated and reconstituted female ldlr^–/– mice with either a mertk^+/+ or mertk^–/– bone marrow. The mice were put on high-fat diet. Mertk deficiency led to increased accumulation of apoptotic cells, promoted a proinflammatory immune response, and accelerated lesion development.

Key Words: apoptosis • atherosclerosis • phagocytosis • inflammation

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Macrophage Function and Its Impact on Atherosclerotic Lesion Composition, Progression, and Stability: The Good, the Bad, and the Ugly

Jeffrey G. Dickhout, Sana Basseri, and Richard C. Austin
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