Matrix Metalloproteinase-14 Deficiency in Bone Marrow–Derived Cells Promotes Collagen Accumulation in Mouse Atherosclerotic Plaques

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Abstract
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...

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