Treatment with 1 to 10 mmol/L N-acetyl-L-cysteine decreased gelatinolytic activity and MMP-9 expression by macrophage-derived foam cells in vitro and in situ.
Does N-acetyl-cysteine decrease gelatinolytic activity and MMP-9 expression in macrophage-derived foam cells from a hypercholesterolemic rabbit model?
N-acetyl-cysteine decreases the matrix-degrading capacity (MMP-9 expression and gelatinolytic activity) of macrophage-derived foam cells, suggesting a potential mechanism to improve atherosclerotic plaque stability.
BACKGROUND: Atherosclerotic plaque destabilization triggers clinical cardiovascular disease and thus represents an attractive therapeutic target. Weakening of tissue through the action of matrix-degrading enzymes, called matrix metalloproteinases (MMPs), released by resident macrophages was previously implicated in unstable vascular syndromes. METHODS AND RESULTS: We used a hypercholesterolemic rabbit model of atherosclerosis to investigate the gelatinolytic activity associated with macrophage-derived foam cells (FCs). Gelatinolytic activity and expression of MMP-9 but not of MMP-2 cosegregated with macrophage FCs in aortic lesions. Macrophage-derived gelatinases were further investigated in vitro. MMP-9 was identified as the main macrophage-derived gelatinase in cells isolated from aortic lesions and from granuloma induced in the same rabbits to increase cell yield. Importantly, detection of activated MMP-9 in the FC culture medium supports the notion that these cells can independently initiate processing of secreted MMP zymogens to active enzymes. We further examined whether FC gelatinolytic activity is dependent on the presence of reactive oxygen species (ROS). We found that treatment (1 to 5 days) with 1 to 10 mmol/L N-acetyl-L-cysteine (NAC), an ROS scavenger, decreased not only gelatinolytic activity but also gelatinase expression by FCs. Similarly, NAC treatment of explanted lesions abolished in situ gelatinolytic activity and MMP-9 expression. CONCLUSIONS: Macrophage FCs are an abundant source of gelatinolytic activity that can be inhibited in vitro and in situ by NAC. This newly described action of antioxidant therapy might prove useful to inhibit matrix degradation and to improve vascular stability.
Galis et al. (Tue,) conducted a other in Atherosclerosis. N-acetyl-L-cysteine (NAC) was evaluated on Gelatinolytic activity and gelatinase expression by macrophage-derived foam cells. Treatment with 1 to 10 mmol/L N-acetyl-L-cysteine decreased gelatinolytic activity and MMP-9 expression by macrophage-derived foam cells in vitro and in situ.