| First Author | Schneider F | Year | 2008 |
| Journal | Circulation | Volume | 117 |
| Issue | 7 | Pages | 931-9 |
| PubMed ID | 18250269 | Mgi Jnum | J:145079 |
| Mgi Id | MGI:3833484 | Doi | 10.1161/CIRCULATIONAHA.107.707448 |
| Citation | Schneider F, et al. (2008) Matrix-metalloproteinase-14 deficiency in bone-marrow-derived cells promotes collagen accumulation in mouse atherosclerotic plaques. Circulation 117(7):931-9 |
| abstractText | BACKGROUND: Interstitial collagen plays a crucial structural role in arteries. Although in vitro results suggest collagenase activity for membrane-bound matrix metalloproteinase type 1 (MMP-14), in vivo evidence for such a function in atherosclerosis remains scant. METHODS AND RESULTS: Because Mmp14-/- mice die by 3 weeks of age, this study used lethally irradiated low-density lipoprotein receptor-deficient mice reconstituted with syngeneic bone marrow cells of Mmp14-/- or Mmp14+/+ mice. In both groups, histological analyses of the aortic root revealed similar plaque size and macrophage and smooth muscle cell content after 8 or 16 weeks of atherogenic diet. By 16 weeks, however, the plaques of low-density lipoprotein receptor-deficient mice engrafted with Mmp14-/- bone marrow (n=12) contained significantly more interstitial collagen than those receiving Mmp14+/+ bone marrow (n=14; P<0.05). In vitro, bone marrow-derived macrophages from Mmp14-/- mice had significantly less interstitial collagenase activity than those from Mmp14+/+ mice both basally (P<0.01) and on tumor necrosis factor-alpha stimulation (P<0.05). Western blot analysis and gelatin zymography of aortic extracts revealed that MMP-14 deficiency yielded decreased activation of pro-MMP-13 but not of pro-MMP-2 or pro-MMP-8. CONCLUSIONS: MMP-14 from bone marrow-derived cells can influence the collagen content of mouse atheroma, a critical component of plaque stability. |
