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Changes in Thrombus Composition and Profilin-1 Release in Acute Myocardial Infarction
Study Questions:
Do levels of profilin-1 (Pfn-1) reflect age of thrombi in the setting of acute myocardial infarction (AMI)?
Methods:
Intracoronary thrombi and blood samples from 86 patients with ST-segment elevation myocardial infarction (STEMI), who underwent thrombectomy, were analyzed. Thrombi were categorized by onset-of-pain-to-percutaneous coronary intervention (PCI) elapsed time (<3 hours [T3] and >6 hours [T6]). Clinical, morphological, and proteomic variables were investigated.
Results:
T3 were mainly composed by platelets and fibrin(ogen), while T6 were characterized by reduced platelet content, and increased leukocyte infiltration with appearance of undifferentiated progenitor cells. Differences between T3 and T6 were found in the cell cytoskeleton-associated proteome (beta-actin and tropomyosin 3 and 4). Using discovery proteomics, Pfn-1 was identified in the coronary thrombi at higher levels in T3 compared to T6. Plasma Pfn-1 levels were low in T3 patients, but increased in both coronary and peripheral circulation in T6 patients indicating release. In vitro platelet aggregation studies showed that platelets secrete Pfn-1 upon complete activation.
Conclusions:
Coronary thrombi show rapid dynamic changes both in structure and cell composition as a function of elapsed onset-of-pain-to-PCI time. Onset-of-pain-to-PCI elapsed time in STEMI patients and hence age of occlusive thrombus can be profiled by Pfn-1 levels found in the peripheral circulation.
Perspective:
This study confirms the dynamic nature of arterial thrombosis over time. Platelet deposition is associated with release of granular proteins into the circulation. Since Pfn-1 appears to be released from platelets and increases with time in the circulation, levels of Pfn-1 may predict age of thrombosis when measured within several hours after STEMI presentation. However, there is marked clinical heterogeneity between patients presenting with MI that likely reflects thrombus heterogeneity. The reproducibility and clinical utility of this measure when applied to a diverse population will require further study.
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