Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis

Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1429-31. doi: 10.1161/ATVBAHA.108.169078. Epub 2008 May 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Atherosclerosis / physiopathology*
  • Disease Models, Animal
  • Female
  • Inflammation / physiopathology
  • Macrophages / physiology*
  • Mice
  • Mice, Knockout
  • Phagocytosis / physiology*
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Receptor Protein-Tyrosine Kinases / deficiency
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, LDL / deficiency
  • c-Mer Tyrosine Kinase

Substances

  • Proto-Oncogene Proteins
  • Receptors, LDL
  • Mertk protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase