C-reactive protein induces expression of matrix metalloproteinase-9: A possible link between inflammation and plaque rupture.

Background: Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute coronary syndromes (ACS). However, little is known about the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP) not only is an independent risk factor for cardiovascular events, but also may exert direct pro-atherosclerotic effects. Therefore, we aimed at determining whether CRP might induce MMP-9 in two different experimental conditions: 1) smooth muscle cells (SMCs) in vitro, and 2) patients with ACS. Methods and results: Effects of increasing concentrations of CRP on MMP-9 expression were evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9 expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9 secretion. In contrast, no differences were found for TIMP-1 protein expression. In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries (controls, n = 21), stable angina (n = 24), and ACS (n = 30). Both MMP-9 and CRP plasma levels were significantly increased across the coronary circulation only in patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP plasma levels was found. Conclusions: CRP induced MMP-9 expression and activity in human SMCs in culture; patients presenting with ACS have increased transcoronary plasma levels of MMP-9 and CRP with a significant correlation between these two markers. This may explain the heightened risk of coronary events in subjects with elevated levels of CRP.