| First Author | van der Vorst EP | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 4 | Pages | 1145-55 |
| PubMed ID | 25659879 | Mgi Jnum | J:220183 |
| Mgi Id | MGI:5632438 | Doi | 10.1016/j.ajpath.2014.11.028 |
| Citation | van der Vorst EP, et al. (2015) Myeloid A Disintegrin and Metalloproteinase Domain 10 Deficiency Modulates Atherosclerotic Plaque Composition by Shifting the Balance from Inflammation toward Fibrosis. Am J Pathol 185(4):1145-55 |
| abstractText | A disintegrin and metalloproteinase domain 10 (ADAM10) is a metalloprotease involved in cleavage of various cell surface molecules, such as adhesion molecules, chemokines, and growth factor receptors. Although we have previously shown an association of ADAM10 expression with atherosclerotic plaque progression, a causal role of ADAM10 in atherosclerosis has not been investigated. Bone marrow from conditional knockout mice lacking Adam10 in the myeloid lineage or from littermate controls was transplanted into lethally irradiated low density lipoprotein receptor Ldlr(-/-) mice on an atherogenic diet. Myeloid Adam10 deficiency did not affect plaque size, but it increased plaque collagen content. Matrix metalloproteinase 9 and 13 expression and matrix metalloproteinase 2 gelatinase activity were significantly impaired in Adam10-deficient macrophages, whereas their capacity to stimulate collagen production was unchanged. Furthermore, relative macrophage content in advanced atherosclerotic lesions was decreased. In vitro, Adam10-deficient macrophages showed reduced migration toward monocyte chemoattractant protein-1 and transmigration through collagen. In addition, Adam10-deficient macrophages displayed increased anti-inflammatory phenotype with elevated IL-10, and reduced production of proinflammatory tumor necrosis factor, IL-12, and nitric oxide in response to lipopolysaccharide. These data suggest a critical role of Adam10 for leukocyte recruitment, inflammatory mediator production, and extracellular matrix degradation. Thereby, myeloid ADAM10 may play a causal role in modulating atherosclerotic plaque stability. |
