Myeloid-related protein-8/14 is critical for the biological response to vascular injury

Circulation. 2009 Aug 4;120(5):427-36. doi: 10.1161/CIRCULATIONAHA.108.814582. Epub 2009 Jul 20.


Background: Myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) are members of the S100 family of calcium-modulated proteins that regulate myeloid cell function and control inflammation, in part, through activation of Toll-like receptor-4 and the receptor for advanced glycation end products. A transcriptional profiling approach in patients with acute coronary syndromes identified MRP-14 as a novel predictor of myocardial infarction. Further studies demonstrated that elevated plasma levels of MRP-8/14 heterodimer predict increased risk of first and recurrent cardiovascular events. Beyond its serving as a risk marker, whether MRP-8/14 participates directly in vascular inflammation and disease remains unclear.

Methods and results: We evaluated vascular inflammation in wild-type and MRP-14-deficient (MRP-14(-/-)) mice that lack MRP-8/14 complexes with experimental arterial injury, vasculitis, or atherosclerosis. After femoral artery wire injury, MRP-14(-/-) mice had significant reductions in leukocyte accumulation, cellular proliferation, and neointimal formation compared with wild-type mice. In a cytokine-induced local Shwartzman-like reaction that produces thrombohemorrhagic vasculitis, MRP-14(-/-) mice had significant reductions in neutrophil accumulation, lesion severity, and hemorrhagic area. In response to high-fat feeding, mice doubly deficient in apolipoprotein E and MRP-8/14 complexes had attenuation in atherosclerotic lesion area and in macrophage accumulation in plaques compared with mice deficient in apolipoprotein E alone.

Conclusions: This study demonstrates that MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure
  • Calgranulin A / genetics
  • Calgranulin A / metabolism*
  • Calgranulin B / genetics
  • Calgranulin B / metabolism*
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / pathology
  • Chemotaxis, Leukocyte / immunology
  • Disease Models, Animal
  • Female
  • Femoral Artery / immunology
  • Femoral Artery / injuries*
  • Femoral Artery / pathology
  • Hemorrhage / immunology
  • Hemorrhage / pathology
  • Humans
  • Lipids / blood
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Monocytes / pathology
  • Neutrophils / pathology
  • Thrombosis / immunology
  • Thrombosis / pathology
  • Tunica Intima / immunology
  • Tunica Intima / injuries
  • Tunica Intima / pathology
  • Vasculitis / immunology*
  • Vasculitis / metabolism*
  • Vasculitis / pathology


  • Calgranulin A
  • Calgranulin B
  • Lipids