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Thrombin engages neutrophil-derived secretion products to upregulate interleukin-6 production in atrial cardiomyocytes and the heart Cover

Thrombin engages neutrophil-derived secretion products to upregulate interleukin-6 production in atrial cardiomyocytes and the heart

Romanian Journal of Cardiology
Volume 35 (2025): Issue 3 (September 2025)
By: Issam Abu-Taha,  Frauke Wiesmann,  Dobromir Dobrev and  Anke C. Fender  
Open Access
|Sep 2025

Figures & Tables

Figure 1

Thrombin does not directly regulate IL-6 in cardiomyocytes at physiological concentrations. (A) Exposure of HL-1 atrial cardiomyocytes to thrombin (Thr, 1 U/ml, 24 h) did not influence either Il6 mRNA expression or (B) IL-6 secretion, compared to control (Ctl, PBS vehicle). (C) Oxidized albumin (oxAlb, 20 ng/mL, 24 h) by contrast increased both Il6 mRNA and (D) secreted IL-6 compared to PBS control in HL-1 cardiomyocytes. Data show mean ± SD.
Thrombin does not directly regulate IL-6 in cardiomyocytes at physiological concentrations. (A) Exposure of HL-1 atrial cardiomyocytes to thrombin (Thr, 1 U/ml, 24 h) did not influence either Il6 mRNA expression or (B) IL-6 secretion, compared to control (Ctl, PBS vehicle). (C) Oxidized albumin (oxAlb, 20 ng/mL, 24 h) by contrast increased both Il6 mRNA and (D) secreted IL-6 compared to PBS control in HL-1 cardiomyocytes. Data show mean ± SD.

Figure 2

Thrombin indirectly regulates cardiomyocyte IL-6 via neutrophil-derived oxidation products. (A) In the presence of thrombin (Thr, 1 U/mL, 3h), human neutrophils in autologous platelet-rich plasma (PRP) produced more extracellular myeloperoxidase (MPO) activity and (B) Advanced Oxidation Protein Products (AOPP) compared to unstimulated control (Ctl) neutrophils. (C) Exposure of HL-1 atrial cardiomyocytes to PRP conditioned with thrombin-stimulated neutrophils increased Il6 transcript levels and (D) IL-6 secretion compared to PRP conditioned with control neutrophils. In the presence of the CD36 inhibitor SSO both effects were attenuated. Data show mean ± SD.
Thrombin indirectly regulates cardiomyocyte IL-6 via neutrophil-derived oxidation products. (A) In the presence of thrombin (Thr, 1 U/mL, 3h), human neutrophils in autologous platelet-rich plasma (PRP) produced more extracellular myeloperoxidase (MPO) activity and (B) Advanced Oxidation Protein Products (AOPP) compared to unstimulated control (Ctl) neutrophils. (C) Exposure of HL-1 atrial cardiomyocytes to PRP conditioned with thrombin-stimulated neutrophils increased Il6 transcript levels and (D) IL-6 secretion compared to PRP conditioned with control neutrophils. In the presence of the CD36 inhibitor SSO both effects were attenuated. Data show mean ± SD.

Figure 3

High fat diet increases myocardial IL-6. (A) Left ventricular (LV) lysates from mice fed a high fat diet (HFD) displayed higher myeloperoxidase (MPO) activity and (B) Advanced Oxidation Protein Products (AOPP) than LV from chow-fed controls. (C) Immunoblot also showed more abundant CD36 and (D) IL-6 total protein expression in LV myocardium of HFD-versus chow-fed mice. Immunoblots were normalized to g-tubulin. Data show mean ± SD. This image was created with Biorender.com.
High fat diet increases myocardial IL-6. (A) Left ventricular (LV) lysates from mice fed a high fat diet (HFD) displayed higher myeloperoxidase (MPO) activity and (B) Advanced Oxidation Protein Products (AOPP) than LV from chow-fed controls. (C) Immunoblot also showed more abundant CD36 and (D) IL-6 total protein expression in LV myocardium of HFD-versus chow-fed mice. Immunoblots were normalized to g-tubulin. Data show mean ± SD. This image was created with Biorender.com.

Figure 4

Schematic depiction of working hypothesis: Thrombin stimulates MPO release and AOPP formation by neutrophils. AOPP uptake via CD36 scavenger receptors provokes IL-6 transcription and secretion by cardiomyocytes, to modulate local inflammatory events.
Schematic depiction of working hypothesis: Thrombin stimulates MPO release and AOPP formation by neutrophils. AOPP uptake via CD36 scavenger receptors provokes IL-6 transcription and secretion by cardiomyocytes, to modulate local inflammatory events.
DOI: https://doi.org/10.2478/rjc-2025-0017 | Journal eISSN: 2734-6382 | Journal ISSN: 1220-658X
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Language: English
Page range: 188 - 193
Published on: Sep 30, 2025
Published by: Romanian Society of Cardiology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Thrombin,
neutrophil,
heart,
atrial cardiomyocyte,
myeloperoxidase,
IL-6,
CD36
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Cardiology,
Surgery,
Cardiac surgery,
Pediatrics and juvenile medicine,
Paediatric cardiology

© 2025 Issam Abu-Taha, Frauke Wiesmann, Dobromir Dobrev, Anke C. Fender, published by Romanian Society of Cardiology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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