Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis.
OBJECTIVE
To study the role of Mer receptor tyrosine kinase (mertk) in atherosclerosis.


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.
Ait-Oufella
Hafid
H
Inserm U689, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France.
Pouresmail
Vahid
V
Simon
Tabassome
T
Blanc-Brude
Olivier
O
Kinugawa
Kiyoka
K
Merval
Régine
R
Offenstadt
Georges
G
Lesèche
Guy
G
Cohen
Philip L
PL
Tedgui
Alain
A
Mallat
Ziad
Z
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050197:Atherosclerosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000172:deficiency; D000076202:c-Mer Tyrosine Kinase
D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase