Metalloproteases 2 and 9, Lp-PLA(2) and Lipoprotein Profile in Coronary Patients

Background And Aims: Many studies suggest that the different steps of the atherosclerotic process may be mediated by metalloproteases (MMPs). MMP-9 and MMP-2, which are highly expressed in the vulnerable regions of the atherosclerotic plaques, have been suggested to be causally involved in plaque rupture. In another manner linked with LDL, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) hydrolyzes phospholipids generating proinflammatory and proatherogenic products. Our aim was to evaluate plasma activity of MMP-2 and 9, as well as Lp-PLA(2), in subjects with coronary artery stenosis in comparison with controls and to correlate these activities with lipoprotein profile and general biomarkers of inflammation.

Methods: Forty two subjects who had undergone coronary angiography were divided into two groups: patients with coronary vessels with at least 45% stenosis (CAD [coronary artery disease], n = 24) and patients without angiographically detectable coronary artery disease (controls, n = 18). Plasma activity of MMP-2 and MMP-9 was measured and correlated with markers of systemic inflammation (hs-CRP), subendothelial inflammation (Lp-PLA(2)) and lipoprotein profile.

Results: Plasma activity of both MMPs was consistently higher in patients than in controls (p <0.01). Pro-MMP-2 (r = 0.34, p <0.01) and MMP-9 (r = 0.51, p <0.02) activities correlated with apoprotein B. Pro-MMP-2 correlated with hs-CRP (r = 0.47, p <0.01) and inversely with HDL cholesterol (r = -0.35, p <0.02). No differences were observed in Lp-PLA(2) between patients and controls (15.2 +/- 4.0 vs. 15.4 +/- 4.5 micromol/mL/h, p = NS, respectively), and no correlation was observed with MMPs.

Conclusions: MMP activity was higher in CAD than in controls. The correlation observed between pro-MMP-2 and high-sensitive C-reactive protein (hs-CRP) may be due to specific systemic inflammatory processes. No correlation was observed between Lp-PLA(2) and MMPs.