Release of MMP-2 in the circulation of patients with acute coronary syndromes undergoing percutaneous coronary intervention: Role of platelets

Abstract

IntroductionMatrix metalloproteinases (MMPs) of atherosclerotic tissue contribute to plaque rupture triggering acute coronary syndromes (ACS). Several MMPs, including MMP-2, are also contained in platelets and released upon activation. An increase in circulating levels of MMP-2 has been reported in patients undergoing percutaneous coronary interventions (PCI), but its time-course and origin remain unclear. Aims of our study were to assess the time-course of MMP-2 release in blood of stable and unstable coronary artery disease patients undergoing PCI and to unravel the possible contribution of platelets to its release. MethodsPeripheral blood samples were drawn immediately before, 4 and 24 h after PCI from patients with ACS (NSTEMI or STEMI, n = 21) or with stable angina (SA, n = 21). Platelet-poor plasma and washed platelet lysates were prepared and stored for subsequent assay of MMP-2 and β-thromboglobulin (β-TG), a platelet-specific protein released upon activation. ResultsPlasma MMP-2 and β-TG increased significantly 4 h after PCI and returned to baseline at 24 h in ACS patients, while they did not change in SA patients. Platelet content of MMP-2 and β-TG decreased significantly 4 h after PCI in patients with ACS, compatible with intravascular platelet activation and release, while they did not change in patients with SA. ConclusionsPCI triggers the release of MMP-2 in the circulation of ACS patients but not in that of patients with SA. Platelets activated by PCI contribute to the increase of plasma MMP-2 releasing their MMP-2 content. Given that previous mechanicistic studies have shown that MMP-2 may sustain platelet activation and unstabilize downstream-located plaques and in the long term favour restenosis and atherosclerosis progression, these data may encourage the search for therapeutic agents blocking MMP-2 release or activity in ACS.