Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients
Microvesicles (MVs) are actively secreted by cells. The NLRP3-inflammasome and the interleukin 6 (IL-6)-pathways are central in cardiovascular disease. Knowledge of how the inflammasome influences the MVs is limited. In a cross-sectional study, we assessed whether MVs in plasma associate with genes...
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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/9/2196 |
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| author | Vibeke Bratseth Jostein Nordeng Ragnhild Helseth Svein Solheim Sissel Åkra Harald Arnesen Gemma Chiva-Blanch Ingebjørg Seljeflot |
| author_facet | Vibeke Bratseth Jostein Nordeng Ragnhild Helseth Svein Solheim Sissel Åkra Harald Arnesen Gemma Chiva-Blanch Ingebjørg Seljeflot |
| author_sort | Vibeke Bratseth |
| collection | DOAJ |
| description | Microvesicles (MVs) are actively secreted by cells. The NLRP3-inflammasome and the interleukin 6 (IL-6)-pathways are central in cardiovascular disease. Knowledge of how the inflammasome influences the MVs is limited. In a cross-sectional study, we assessed whether MVs in plasma associate with genes encoding inflammasome signalling in coronary thrombi. Moreover, any relationships between inflammasome activation and phosphatidylserine (PS) externalization, determined through Annexin V (AV<sup>+</sup>) labelling, and myocardial injury, assessed by cardiac troponin T (cTnT), were analysed. Intracoronary thrombi and blood samples from STEMI patients (<i>n</i> = 33) were investigated. mRNA of NLRP3, caspase-1, interleukin-1β (IL-1β), interleukin-18 (IL-18), IL-6, soluble IL-6-receptor (sIL-6R), and glycoprotein-130 (gp130) were isolated from the thrombi and relatively quantified by RT-PCR. MVs were analysed by flow cytometry. Total AV<sup>+</sup> MVs, mainly reflecting hypercoagulability, correlated positively to NLRP3 gene expression (r = 0.545, <i>p</i> = 0.009). A similar pattern was seen for platelet, endothelial and leukocyte derived MVs, separately. The majority of the MVs were AV<sup>−</sup> (96%). Total and AV<sup>−</sup> MVs correlated inversely with IL-1β (r = −0.399 and −0.438, respectively, <i>p</i> < 0.05, both) and gp130 (r = −0.457 and −0.502, respectively, <i>p</i> < 0.05, both). No correlations between MVs and cTnT were observed. Our findings indicate an association between NLRP3-inflammasome in coronary thrombi and procoagulant AV<sup>+</sup> MVs in STEMI patients. The inverse relationships between AV<sup>−</sup> MVs and the gene expression of inflammasome activation may indicate an immuno-dampening role of this subpopulation. |
| first_indexed | 2024-03-10T00:39:10Z |
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| institution | Directory Open Access Journal |
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| spelling | doaj.art-5170618f5c8e4102862964d41826045a2023-11-23T15:10:44ZengMDPI AGBiomedicines2227-90592022-09-01109219610.3390/biomedicines10092196Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI PatientsVibeke Bratseth0Jostein Nordeng1Ragnhild Helseth2Svein Solheim3Sissel Åkra4Harald Arnesen5Gemma Chiva-Blanch6Ingebjørg Seljeflot7Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayDepartment of Endocrinology and Nutrition, August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Hospital Clinic of Barcelona, 08036 Barcelona, SpainCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, 0424 Oslo, NorwayMicrovesicles (MVs) are actively secreted by cells. The NLRP3-inflammasome and the interleukin 6 (IL-6)-pathways are central in cardiovascular disease. Knowledge of how the inflammasome influences the MVs is limited. In a cross-sectional study, we assessed whether MVs in plasma associate with genes encoding inflammasome signalling in coronary thrombi. Moreover, any relationships between inflammasome activation and phosphatidylserine (PS) externalization, determined through Annexin V (AV<sup>+</sup>) labelling, and myocardial injury, assessed by cardiac troponin T (cTnT), were analysed. Intracoronary thrombi and blood samples from STEMI patients (<i>n</i> = 33) were investigated. mRNA of NLRP3, caspase-1, interleukin-1β (IL-1β), interleukin-18 (IL-18), IL-6, soluble IL-6-receptor (sIL-6R), and glycoprotein-130 (gp130) were isolated from the thrombi and relatively quantified by RT-PCR. MVs were analysed by flow cytometry. Total AV<sup>+</sup> MVs, mainly reflecting hypercoagulability, correlated positively to NLRP3 gene expression (r = 0.545, <i>p</i> = 0.009). A similar pattern was seen for platelet, endothelial and leukocyte derived MVs, separately. The majority of the MVs were AV<sup>−</sup> (96%). Total and AV<sup>−</sup> MVs correlated inversely with IL-1β (r = −0.399 and −0.438, respectively, <i>p</i> < 0.05, both) and gp130 (r = −0.457 and −0.502, respectively, <i>p</i> < 0.05, both). No correlations between MVs and cTnT were observed. Our findings indicate an association between NLRP3-inflammasome in coronary thrombi and procoagulant AV<sup>+</sup> MVs in STEMI patients. The inverse relationships between AV<sup>−</sup> MVs and the gene expression of inflammasome activation may indicate an immuno-dampening role of this subpopulation.https://www.mdpi.com/2227-9059/10/9/2196microvesiclesNLRP3 inflammasomeIL-6 signalling pathwayST-elevation myocardial infarctionAnnexin Vimmunothrombosis |
| spellingShingle | Vibeke Bratseth Jostein Nordeng Ragnhild Helseth Svein Solheim Sissel Åkra Harald Arnesen Gemma Chiva-Blanch Ingebjørg Seljeflot Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients Biomedicines microvesicles NLRP3 inflammasome IL-6 signalling pathway ST-elevation myocardial infarction Annexin V immunothrombosis |
| title | Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients |
| title_full | Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients |
| title_fullStr | Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients |
| title_full_unstemmed | Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients |
| title_short | Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients |
| title_sort | circulating microvesicles in association with the nlrp3 inflammasome in coronary thrombi from stemi patients |
| topic | microvesicles NLRP3 inflammasome IL-6 signalling pathway ST-elevation myocardial infarction Annexin V immunothrombosis |
| url | https://www.mdpi.com/2227-9059/10/9/2196 |
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