Human cytomegalovirus (HCMV) has been suggested to contribute to the development of
vascular diseases. Since
matrix metalloproteinases (
MMPs) have been implicated in
atherosclerosis and plaque
rupture, we investigated the effect of HCMV
infection on
MMP expression in human macrophages. We used quantitative real-time PCR, Western blotting, and
gelatin zymography to study the expression and activity of MMP-2, -3, -7, -9, -12, -13, and -14 and of
tissue inhibitor of metalloproteinase 1 (TIMP-1), -2, -3, and -4. HCMV
infection reduced MMP-9
mRNA,
protein, and activity levels but increased
TIMP-1 mRNA and
protein levels. Furthermore, a decrease in MMP-12, MMP-14,
TIMP-2, and
TIMP-3 mRNA levels could be detected. The MMP-9 and
TIMP-1 mRNA alterations required viral replication. MMP-9
mRNA expression was affected by an immediate-early or early viral gene product, whereas
TIMP-1 mRNA expression was affected by late
viral gene products. We conclude that HCMV
infection specifically alters the
MMP-9/TIMP-1 balance in human macrophages, which in turn reduces MMP-9 activity in infected cells. Since MMP-9 prevents
atherosclerotic plaque development in mice, these results suggest that HCMV may contribute to
atherogenesis through specific effects on MMP-9 activity.