Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress

被引：26

作者：

Cedervall, J. ^{[1
]}

Herre, M. ^{[1
]}

Dragomir, A. ^{[2
]}

Rabelo-Melo, F. ^{[1
]}

Svensson, A. ^{[3
,4
]}

Thalin, C. ^{[5
]}

Rosell, A. ^{[5
]}

Hjalmar, V ^{[5
,6
]}

Wallen, H. ^{[5
]}

Lindman, H. ^{[2
]}

Pejler, G. ^{[1
]}

Hagstrom, E. ^{[7
]}

Hultstrom, M. ^{[3
,4
]}

Larsson, A. ^{[7
]}

Olsson, A. K. ^{[1
]}

机构：

[1] Uppsala Univ, Biomed Ctr, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden

[2] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[3] Uppsala Univ, Dept Med Cell Biol, Integrat Physiol, Uppsala, Sweden

[4] Uppsala Univ, Dept Surg Sci Anaesthesiol & Intens Care Med, Uppsala, Sweden

[5] Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden

[6] Danderyd Hosp, Diagnost Ctr, Karolinska Inst, Stockholm, Sweden

[7] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

来源：

ONCOIMMUNOLOGY | 2022年 / 11卷 / 01期

基金：

瑞典研究理事会;

关键词：

Neutrophil extracellular traps; NETs; cancer; cardiac; hypertrophy; inflammation; RENAL-INSUFFICIENCY; VENOUS THROMBOSIS; TISSUE FACTOR; HEART; BIOMARKERS; NETOSIS; RISK; DNA; EXPRESSION; PREVENTION;

D O I：

10.1080/2162402X.2022.2049487

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naive individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naive cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.

引用

页数：14

共 64 条

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