Dataset Information

Chronic inflammatory effects of in vivo irradiation of the murine heart on endothelial cells mimic mechanisms involved in atherosclerosis.

ABSTRACT:

Purpose

Radiotherapy is a major pillar in the treatment of solid tumors including breast cancer. However, epidemiological studies have revealed an increase in cardiac diseases approximately a decade after exposure of the thorax to ionizing irradiation, which might be related to vascular inflammation. Therefore, chronic inflammatory effects were examined in primary heart and lung endothelial cells (ECs) of mice after local heart irradiation.

Methods

Long-lasting effects on primary ECs of the heart and lung were studied 20-50 weeks after local irradiation of the heart of mice (8 and 16 Gy) in vivo by multiparameter flow cytometry using antibodies directed against cell surface markers related to proliferation, stemness, lipid metabolism, and inflammation, and compared to those induced by occlusion of the left anterior descending coronary artery.

Results

In vivo irradiation of the complete heart caused long-lasting persistent upregulation of inflammatory (HCAM, ICAM‑1, VCAM-1), proliferation (CD105), and lipid (CD36) markers on primary heart ECs and an upregulation of ICAM‑1 and VCAM‑1 on primary ECs of the partially irradiated lung lobe. An artificially induced heart infarction induces similar effects with respect to inflammatory markers, albeit in a shorter time period.

Conclusion

The long-lasting upregulation of prominent inflammatory markers on primary heart and lung ECs suggests that local heart irradiation induces chronic inflammation in the microvasculature of the heart and partially irradiated lung that leads to cardiac injury which might be related to altered lipid metabolism in the heart.

SUBMITTER: Wittmann A

PROVIDER: S-EPMC10673733 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Chronic inflammatory effects of in vivo irradiation of the murine heart on endothelial cells mimic mechanisms involved in atherosclerosis.

Wittmann Andrea A Bartels Anna A Alkotub Bayan B Bauer Lisa L Kafshgari Morteza Hasanzadeh MH Multhoff Gabriele G

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 20230902 12

<h4>Purpose</h4>Radiotherapy is a major pillar in the treatment of solid tumors including breast cancer. However, epidemiological studies have revealed an increase in cardiac diseases approximately a decade after exposure of the thorax to ionizing irradiation, which might be related to vascular inflammation. Therefore, chronic inflammatory effects were examined in primary heart and lung endothelial cells (ECs) of mice after local heart irradiation.<h4>Methods</h4>Long-lasting effects on primary ...[more]

PMID: 37658922

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Project description:Thoracic radiotherapy is an effective treatment for many types of cancer; however it is also associated with an increased risk of developing cardiovascular disease (CVD), appearing mainly ≥10 years after radiation exposure. The present study investigated acute and early term physiological and molecular changes in the cardiovascular system after ionizing radiation exposure. Female and male ApoE‑/‑ mice received a single exposure of low or high dose X‑ray thoracic irradiation (0.1 and 10 Gy). The level of cholesterol and triglycerides, as well as a large panel of inflammatory markers, were analyzed in serum samples obtained at 24 h and 1 month after irradiation. The secretion of inflammatory markers was further verified in vitro in coronary artery and microvascular endothelial cell lines after exposure to low and high dose of ionizing radiation (0.1 and 5 Gy). Local thoracic irradiation of ApoE‑/‑ mice increased serum growth differentiation factor‑15 (GDF‑15) and C‑X‑C motif chemokine ligand 10 (CXCL10) levels in both female and male mice 24 h after high dose irradiation, which were also secreted from coronary artery and microvascular endothelial cells in vitro. Sex‑specific responses were observed for triglyceride and cholesterol levels, and some of the assessed inflammatory markers as detailed below. Male ApoE‑/‑ mice demonstrated elevated intercellular adhesion molecule‑1 and P‑selectin at 24 h, and adiponectin and plasminogen activator inhibitor‑1 at 1 month after irradiation, while female ApoE‑/‑ mice exhibited decreased monocyte chemoattractant protein‑1 and urokinase‑type plasminogen activator receptor at 24 h, and basic fibroblast growth factor 1 month after irradiation. The inflammatory responses were mainly significant following high dose irradiation, but certain markers showed significant changes after low dose exposure. The present study revealed that acute/early inflammatory responses occurred after low and high dose thoracic irradiation. However, further research is required to elucidate early asymptomatic changes in the cardiovascular system post thoracic X‑irradiation and to investigate whether GDF‑15 and CXCL10 could be considered as potential biomarkers for the early detection of CVD risk in thoracic radiotherapy‑treated patients.

Dataset Information

Chronic inflammatory effects of in vivo irradiation of the murine heart on endothelial cells mimic mechanisms involved in atherosclerosis.

Purpose

Methods

Results

Conclusion

Publications

Chronic inflammatory effects of in vivo irradiation of the murine heart on endothelial cells mimic mechanisms involved in atherosclerosis.

Similar Datasets

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