Gene expression of fibrinolytic markers in coronary thrombi

Jostein Nordeng; Svein Solheim; Sissel Åkra; Hossein Schandiz; Pavel Hoffmann; Borghild Roald; Bjørn Bendz; Harald Arnesen; Ragnhild Helseth; Ingebjørg Seljeflot

doi:10.1186/s12959-022-00383-1

Gene expression of fibrinolytic markers in coronary thrombi

Thromb J. 2022 Apr 29;20(1):23. doi: 10.1186/s12959-022-00383-1.

Authors

Jostein Nordeng^{1

2

3}, Svein Solheim^{4

5}, Sissel Åkra⁴, Hossein Schandiz⁶, Pavel Hoffmann⁷, Borghild Roald^{8

9}, Bjørn Bendz^{8

10}, Harald Arnesen^{4

8}, Ragnhild Helseth^{4

5}, Ingebjørg Seljeflot^{4

5

8}

Affiliations

¹ Center for Clinical Heart Research, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway. drnordeng@gmail.com.
² Department of Cardiology, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway. drnordeng@gmail.com.
³ Faculty of Medicine, University of Oslo, Klaus Torgårds vei 3, Pb 1078 Blindern, 0316, Oslo, Norway. drnordeng@gmail.com.
⁴ Center for Clinical Heart Research, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway.
⁵ Department of Cardiology, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway.
⁶ Department of Pathology, Akershus University Hospital, Sykehusveien 25, Pb1000, 1478, Lørenskog, Norway.
⁷ Section for Interventional Cardiology, Department of Cardiology, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway.
⁸ Faculty of Medicine, University of Oslo, Klaus Torgårds vei 3, Pb 1078 Blindern, 0316, Oslo, Norway.
⁹ Department of Pathology, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway.
¹⁰ Department of Cardiology, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, Pb 4950 Nydalen, N-0424, Oslo, Norway.

Abstract

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 .

Keywords: Coronary thrombi; Fibrinolytic system; Genetic expression; ST-elevation infarction.

Associated data

ClinicalTrials.gov/NCT02746822