Key result
Genes encoding tPA, uPA, PAI-1, and PAI-2 were highly expressed in 74-97% of coronary thrombi from STEMI patients and correlated significantly with the presence of monocytes/macrophages.
Why the study?
The fibrinolytic system is important in atherothrombosis, but whether genes encoding tPA, uPA, PAI-1, and PAI-2 are expressed in coronary thrombi from acute STEMI patients was unknown.
Does the gene expression of fibrinolytic markers in coronary thrombi correlate with myocardial injury or inflammatory cell presence in STEMI patients?
Cross-Sectional (n=33)
No
Does the gene expression of fibrinolytic markers in coronary thrombi correlate with myocardial injury or inflammatory cell presence in STEMI patients?
Fibrinolytic regulator genes are highly expressed in coronary thrombi of STEMI patients and correlate with local inflammatory cells (monocytes/macrophages) rather than myocardial injury.
Local fibrinolytic gene expression in coronary thrombi may modulate STEMI outcomes; leaves open clinical relevance beyond circulating PAI-1.
BACKGROUND: The fibrinolytic system plays an important role in coronary artery atherothrombosis, and especially circulating plasminogen-activator inhibitor (PAI) type 1 (PAI-1) associates with increased mortality, infarct size and heart failure in patients with myocardial infarction (MI). In a cross-sectional study, we aimed to study whether genes encoding tissue plasminogen activator (tPA), urinary-type plasminogen activator (uPA), PAI-1 and PAI-2 are expressed in coronary thrombi from acute ST-elevation MI (STEMI) patients. Any relations to myocardial injury measured by peak troponin T, time from symptom onset to Percutaneous Coronary Intervention (PCI), and to different cell types present in the thrombi were also explored. METHODS: Intracoronary thrombi were aspirated from 33 STEMI patients treated with primary PCI. The thrombi were snap-frozen for gene expression analyses, relatively quantified by RT PCR. Peripheral blood samples were drawn. Correlations were performed by Spearmans rho. RESULTS: The genes were present in 74-94% of the thrombi. Median peak troponin T was 3434 μ/L and median ischemic time 152 min. There were no significant correlations between the measured genes and troponin T, or ischemic time. Genes encoding tPA, u-PA, PAI-1 and PAI-2 all correlated significantly to the presence of monocytes/macrophages (CD68) in the thrombi (p = 0.028, p < 0.001, p = 0.003, p < 0.001). PAI-1 and PAI-2 also correlated to endothelial cells (CD31) (p = 0.002, p = 0.016). uPA associated with neutrophil granulocytes (CD 66b) (p = 0.019). CONCLUSION: Genes encoding tPA, uPA, PAI-1 and PAI-2 were highly expressed in human coronary thrombi from STEMI patients, indicating fibrinolytic regulators playing active roles in the thrombi, although not related to myocardial injury. All markers related to the presence of monocytes/macrophages, indicating connection to local inflammatory cells. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov with identification number NCT02746822 .
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Nordeng et al. (2022) conducted a cross-sectional in ST-elevation myocardial infarction (STEMI) (n=33). Fibrinolytic markers (tPA, uPA, PAI-1, PAI-2) gene expression was evaluated on Presence of genes encoding tPA, uPA, PAI-1 and PAI-2 in coronary thrombi and correlation to myocardial injury, ischemic time, and cell types. Genes encoding tPA, uPA, PAI-1, and PAI-2 were highly expressed in 74-97% of coronary thrombi from STEMI patients and correlated significantly with the presence of monocytes/macrophages.
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