Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms
© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd..
BACKGROUND: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis.
OBJECTIVES: Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well.
METHODS: Using whole blood gene expression profiling in patients with essential thrombocythemia (ET; n = 19), polycythemia vera (PV; n = 41), or primary myelofibrosis (PMF; n = 9), we herein for the first time report aberrant expression of several atherosclerosis genes.
RESULTS: Of 84 atherosclerosis genes, 45, 56, and 46 genes were deregulated in patients with ET, PV, or PMF, respectively. Furthermore, BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated and BCL2 progressively significantly downregulated from ET over PV to PMF (all FDR <0.05).
CONCLUSIONS: We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:111 |
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| Enthalten in: |
European journal of haematology - 111(2023), 5 vom: 12. Nov., Seite 805-814 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Skov, Vibe [VerfasserIn] |
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| Links: |
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| Themen: |
Cardiovascular disease |
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| Anmerkungen: |
Date Revised 02.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/ejh.14081 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms |
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| 500 | |a Date Revised 02.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis | ||
| 520 | |a OBJECTIVES: Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well | ||
| 520 | |a METHODS: Using whole blood gene expression profiling in patients with essential thrombocythemia (ET; n = 19), polycythemia vera (PV; n = 41), or primary myelofibrosis (PMF; n = 9), we herein for the first time report aberrant expression of several atherosclerosis genes | ||
| 520 | |a RESULTS: Of 84 atherosclerosis genes, 45, 56, and 46 genes were deregulated in patients with ET, PV, or PMF, respectively. Furthermore, BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated and BCL2 progressively significantly downregulated from ET over PV to PMF (all FDR <0.05) | ||
| 520 | |a CONCLUSIONS: We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MPNs | |
| 650 | 4 | |a cardiovascular disease | |
| 650 | 4 | |a chronic inflammation | |
| 650 | 4 | |a deregulation of atherosclerosis genes | |
| 650 | 4 | |a whole blood gene expression profiling | |
| 700 | 1 | |a Thomassen, Mads |e verfasserin |4 aut | |
| 700 | 1 | |a Kjaer, Lasse |e verfasserin |4 aut | |
| 700 | 1 | |a Larsen, Morten Kranker |e verfasserin |4 aut | |
| 700 | 1 | |a Knudsen, Trine A |e verfasserin |4 aut | |
| 700 | 1 | |a Ellervik, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Kruse, Torben A |e verfasserin |4 aut | |
| 700 | 1 | |a Hasselbalch, Hans Carl |e verfasserin |4 aut | |
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