Expression of Neutrophil Collagenase (Matrix Metalloproteinase-8) in Human Atheroma A Novel Collagenolytic Pathway Suggested by Transcriptional Profiling

Background Loss of interstitial collagen, particularly type I collagen, the major load-bearing molecule of atherosclerotic plaques, renders atheroma prone to rupture. Initiation of collagen breakdown requires interstitial collagenases, a matrix metalloproteinase (MMP) subfamily consisting of MMP-1, MMP-8, and MMP-13. Previous work demonstrated the overexpression of MMP-1 and MMP-13 in human atheroma. However, no study has yet evaluated the expression of MMP-8, known as “neutrophil collagenase,” the enzyme that preferentially degrades type I collagen, because granulocytes do not localize in plaques. Methods and Results Transcriptional profiling and reverse transcription–polymerase chain reaction analysis revealed inducible expression of MMP-8 transcripts in CD40 ligand–stimulated mononuclear phagocytes. Western blot analysis demonstrated that 3 atheroma-associated cell types, namely, endothelial cells, smooth muscle cells, and mononuclear phagocytes, expressed MMP-8 in vitro upon stimulation with proinflam...