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

Autor: Peter Libby, Fabrice Schneider, James P. Canner, Norbert Gerdes, Sai Man Timothy Tang, Guo-Ping Shi, Galina K. Sukhova, Masanori Aikawa, Suneel S. Apte
Rok vydání: 2008
Předmět:
Zdroj: Circulation. 117:931-939
ISSN: 1524-4539
0009-7322
Popis: 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 Mmp14 −/− mice had significantly less interstitial collagenase activity than those from Mmp14 +/+ mice both basally ( P P Conclusion— MMP-14 from bone marrow–derived cells can influence the collagen content of mouse atheroma, a critical component of plaque stability.
Databáze: OpenAIRE