| First Author | Croce K | Year | 2009 |
| Journal | Circulation | Volume | 120 |
| Issue | 5 | Pages | 427-36 |
| PubMed ID | 19620505 | Mgi Jnum | J:166419 |
| Mgi Id | MGI:4844253 | Doi | 10.1161/CIRCULATIONAHA.108.814582 |
| Citation | Croce K, et al. (2009) Myeloid-related protein-8/14 is critical for the biological response to vascular injury. Circulation 120(5):427-36 |
| abstractText | 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. |
