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

Introduction: Matrix 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. Methods: Peripheral 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 8-thromboglobulin (8-TG), a platelet-specific protein released upon activation. Results: Plasma MMP-2 and 8-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 8-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. Conclusions: PCI 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.

Automated summary

This study aimed to assess the time-course of MMP-2 release during PCI and the contribution of platelets to its release. The results showed that PCI triggers the release of MMP-2 in ACS patients but not in SA patients.