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Published on: February 13, 2013
Gene expression of fibrinolytic markers in coronary thrombi
Jostein Nordeng1,2,3, Svein Solheim4,5, Sissel Åkra4
1Center for Clinical Heart Research, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway. drnordeng@gmail.com.
Insights
Genes for fibrinolytic regulators like PAI-1 were found in coronary thrombi of ST-elevation MI patients. These genes correlated with inflammatory cells, not heart injury, suggesting localized roles in thrombosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Thrombosis Research
Background:
- The fibrinolytic system is crucial in coronary artery atherothrombosis.
- Plasminogen-activator inhibitor type 1 (PAI-1) is linked to adverse outcomes in myocardial infarction (MI).
- Investigating fibrinolytic gene expression in acute coronary thrombi is vital.
Purpose of the Study:
- To determine the expression of tissue plasminogen activator (tPA), urinary-type plasminogen activator (uPA), PAI-1, and PAI-2 genes in coronary thrombi from ST-elevation MI (STEMI) patients.
- To explore correlations between these gene expressions and myocardial injury markers (peak troponin T), ischemic times, and thrombus cellular composition.
Main Methods:
- Gene expression analysis using RT PCR on intracoronary thrombi aspirated from 33 STEMI patients.
- Relative gene quantification and correlation analysis (Spearman's rho) with clinical and cellular data.
- Comparison with peripheral blood samples and thrombus cellular markers (CD68, CD31, CD66b).
Main Results:
- Genes for tPA, uPA, PAI-1, and PAI-2 were highly expressed in 74-94% of STEMI thrombi.
- No significant correlations were found between gene expression and peak troponin T or ischemic time.
- All studied genes significantly correlated with the presence of monocytes/macrophages; PAI-1/PAI-2 with endothelial cells; uPA with neutrophils.
Conclusions:
- Fibrinolytic regulator genes are actively expressed within human coronary thrombi in STEMI.
- The expression of these genes is linked to local inflammatory cell infiltration, particularly monocytes/macrophages.
- Despite high expression, these genes did not correlate with the extent of myocardial injury in this cohort.
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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