Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

Sarah S Poulsen; Anne T Saber; Alicja Mortensen; Józef Szarek; Dongmei Wu; Andrew Williams; Ole Andersen; Nicklas R Jacobsen; Carole L Yauk; Erik Håkan Richard Wallin; Sabina Halappanavar; Ulla Vogel

doi:10.1016/j.taap.2015.01.011

Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

Sarah S Poulsen, Anne T Saber, Alicja Mortensen, Józef Szarek, Dongmei Wu, Andrew Williams, Ole Andersen, Nicklas R Jacobsen, Carole L Yauk, Erik Håkan Richard Wallin, Sabina Halappanavar, Ulla Vogel

Institut for Folkesundhedsvidenskab

45 Citationer (Scopus)

Abstract

Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162μg/mouse of small, entangled (CNTSmall, 0.8±0.1μm long) or large, thick MWCNTs (CNTLarge, 4±0.4μm long). Liver tissues and plasma were harvested 1, 3 and 28days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease.

Originalsprog	Engelsk
Tidsskrift	Toxicology and Applied Pharmacology
Vol/bind	283
Udgave nummer	3
Sider (fra-til)	210-222
Antal sider	13
ISSN	0041-008X
DOI	https://doi.org/10.1016/j.taap.2015.01.011
Status	Udgivet - 5 mar. 2015

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10.1016/j.taap.2015.01.011Licens: CC BY-NC-ND

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Poulsen, S. S., Saber, A. T., Mortensen, A., Szarek, J., Wu, D., Williams, A., Andersen, O., Jacobsen, N. R., Yauk, C. L., Wallin, E. H. R., Halappanavar, S., & Vogel, U. (2015). Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease. Toxicology and Applied Pharmacology, 283(3), 210-222. https://doi.org/10.1016/j.taap.2015.01.011

Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease. / Poulsen, Sarah S; Saber, Anne T; Mortensen, Alicja et al.

I: Toxicology and Applied Pharmacology, Bind 283, Nr. 3, 05.03.2015, s. 210-222.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Poulsen, SS, Saber, AT, Mortensen, A, Szarek, J, Wu, D, Williams, A, Andersen, O, Jacobsen, NR, Yauk, CL, Wallin, EHR, Halappanavar, S & Vogel, U 2015, 'Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease', Toxicology and Applied Pharmacology, bind 283, nr. 3, s. 210-222. https://doi.org/10.1016/j.taap.2015.01.011

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title = "Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease",

abstract = "Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162μg/mouse of small, entangled (CNTSmall, 0.8±0.1μm long) or large, thick MWCNTs (CNTLarge, 4±0.4μm long). Liver tissues and plasma were harvested 1, 3 and 28days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease.",

keywords = "Acute-Phase Proteins, Acute-Phase Reaction, Animals, Biomarkers, Cardiovascular Diseases, Cholesterol, Female, Gene Expression Regulation, Homeostasis, Inflammation Mediators, Inhalation Exposure, Liver, Mice, Inbred C57BL, Nanotubes, Carbon, Particle Size, RNA, Messenger, Risk Assessment, Time Factors",

author = "Poulsen, {Sarah S} and Saber, {Anne T} and Alicja Mortensen and J{\'o}zef Szarek and Dongmei Wu and Andrew Williams and Ole Andersen and Jacobsen, {Nicklas R} and Yauk, {Carole L} and Wallin, {Erik H{\aa}kan Richard} and Sabina Halappanavar and Ulla Vogel",

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doi = "10.1016/j.taap.2015.01.011",

language = "English",

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T1 - Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

AU - Poulsen, Sarah S

AU - Saber, Anne T

AU - Mortensen, Alicja

AU - Szarek, Józef

AU - Wu, Dongmei

AU - Williams, Andrew

AU - Andersen, Ole

AU - Jacobsen, Nicklas R

AU - Yauk, Carole L

AU - Wallin, Erik Håkan Richard

AU - Halappanavar, Sabina

AU - Vogel, Ulla

PY - 2015/3/5

Y1 - 2015/3/5

N2 - Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162μg/mouse of small, entangled (CNTSmall, 0.8±0.1μm long) or large, thick MWCNTs (CNTLarge, 4±0.4μm long). Liver tissues and plasma were harvested 1, 3 and 28days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease.

AB - Adverse lung effects following pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) are well documented in rodents. However, systemic effects are less understood. Epidemiological studies have shown increased cardiovascular disease risk after pulmonary exposure to airborne particles, which has led to concerns that inhalation exposure to MWCNTs might pose similar risks. We analyzed parameters related to cardiovascular disease, including plasma acute phase response (APR) proteins and plasma lipids, in female C57BL/6 mice exposed to a single intratracheal instillation of 0, 18, 54 or 162μg/mouse of small, entangled (CNTSmall, 0.8±0.1μm long) or large, thick MWCNTs (CNTLarge, 4±0.4μm long). Liver tissues and plasma were harvested 1, 3 and 28days post-exposure. In addition, global hepatic gene expression, hepatic cholesterol content and liver histology were used to assess hepatic effects. The two MWCNTs induced similar systemic responses despite their different physicochemical properties. APR proteins SAA3 and haptoglobin, plasma total cholesterol and low-density/very low-density lipoprotein were significantly increased following exposure to either MWCNTs. Plasma SAA3 levels correlated strongly with pulmonary Saa3 levels. Analysis of global gene expression revealed perturbation of the same biological processes and pathways in liver, including the HMG-CoA reductase pathway. Both MWCNTs induced similar histological hepatic changes, with a tendency towards greater response following CNTLarge exposure. Overall, we show that pulmonary exposure to two different MWCNTs induces similar systemic and hepatic responses, including changes in plasma APR, lipid composition, hepatic gene expression and liver morphology. The results link pulmonary exposure to MWCNTs with risk of cardiovascular disease.

KW - Acute-Phase Proteins

KW - Acute-Phase Reaction

KW - Animals

KW - Biomarkers

KW - Cardiovascular Diseases

KW - Cholesterol

KW - Female

KW - Gene Expression Regulation

KW - Homeostasis

KW - Inflammation Mediators

KW - Inhalation Exposure

KW - Liver

KW - Mice, Inbred C57BL

KW - Nanotubes, Carbon

KW - Particle Size

KW - RNA, Messenger

KW - Risk Assessment

KW - Time Factors

U2 - 10.1016/j.taap.2015.01.011

DO - 10.1016/j.taap.2015.01.011

M3 - Journal article

C2 - 25620056

SN - 0041-008X

VL - 283

SP - 210

EP - 222

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

IS - 3

ER -

Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease

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