This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/8/1429    most recent ATVBAHA.108.169078v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ait-Oufella, H. Articles by Mallat, Z. Search for Related Content PubMed PubMed Citation Articles by Ait-Oufella, H. Articles by Mallat, Z. Related Collections Related Article

(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

Related Article:

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
Arterioscler Thromb Vasc Biol 2008 28: 1413-1415. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				S. Li, Y. Sun, C.-P. Liang, E. B. Thorp, S. Han, A. W. Jehle, V. Saraswathi, B. Pridgen, J. E. Kanter, R. Li, et al. Defective Phagocytosis of Apoptotic Cells by Macrophages in Atherosclerotic Lesions of ob/ob Mice and Reversal by a Fish Oil Diet Circ. Res., November 20, 2009; 105(11): 1072 - 1082. [Abstract] [Full Text] [PDF]

				E. Thorp and I. Tabas Mechanisms and consequences of efferocytosis in advanced atherosclerosis J. Leukoc. Biol., November 1, 2009; 86(5): 1089 - 1095. [Abstract] [Full Text] [PDF]

				T. Seimon and I. Tabas Mechanisms and consequences of macrophage apoptosis in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S382 - S387. [Abstract] [Full Text] [PDF]

				Z. Mallat, S. Taleb, H. Ait-Oufella, and A. Tedgui The role of adaptive T cell immunity in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S364 - S369. [Abstract] [Full Text] [PDF]

				D. T. Bolick, M. D. Skaflen, L. E. Johnson, S.-C. Kwon, D. Howatt, A. Daugherty, K. S. Ravichandran, and C. C. Hedrick G2A Deficiency in Mice Promotes Macrophage Activation and Atherosclerosis Circ. Res., February 13, 2009; 104(3): 318 - 327. [Abstract] [Full Text] [PDF]

				M. C.H. Clarke and M. R. Bennett Cause or Consequence: What Does Macrophage Apoptosis Do in Atherosclerosis? Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 153 - 155. [Full Text] [PDF]

				D. Liao, X. Wang, M. Li, P. H. Lin, Q. Yao, and C. Chen Human protein S inhibits the uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human macrophages Blood, January 1, 2009; 113(1): 165 - 174. [Abstract] [Full Text] [PDF]

				J. G. Dickhout, S. Basseri, and R. C. Austin Macrophage Function and Its Impact on Atherosclerotic Lesion Composition, Progression, and Stability: The Good, the Bad, and the Ugly Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1413 - 1415. [Full Text] [PDF]