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, Jozef Szarek, Dongmei Wu, Andrew Williams, Ole Andersen, Nicklas R. Jacobsen, Carole L. Yauk, Hakan Wallin, Sabina Halappanavar, Ulla Birgitte Vogel

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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 162 mu g/mouse of small, entangled (CNTsmall, 0.8 +/- 0.1 pm long) or large, thick MWCNTs (CNTLarge, 4 +/- 0.4 mu m long). Liver tissues and plasma were harvested 1,3 and 28 days 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. (C) 2015 The Authors. Published by Elsevier Inc.
Original languageEnglish
JournalToxicology and Applied Pharmacology
Volume283
Issue number3
Pages (from-to)210-222
Number of pages13
ISSN0041-008X
DOIs
Publication statusPublished - 2015

Bibliographical note

© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

Keywords

  • Nanotoxicology
  • Atherosclerosis
  • Toxicogenomics
  • Liver
  • Acute phase response
  • Histology

Cite this

Poulsen, Sarah S. ; Saber, Anne T. ; Mortensen, Alicja ; Szarek, Jozef ; Wu, Dongmei ; Williams, Andrew ; Andersen, Ole ; Jacobsen, Nicklas R. ; Yauk, Carole L. ; Wallin, Hakan ; Halappanavar, Sabina ; Vogel, Ulla Birgitte. / Changes in cholesterol homeostasis and acute phase response link pulmonary exposure to multi-walled carbon nanotubes to risk of cardiovascular disease. In: Toxicology and Applied Pharmacology. 2015 ; Vol. 283, No. 3. pp. 210-222.
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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 162 mu g/mouse of small, entangled (CNTsmall, 0.8 +/- 0.1 pm long) or large, thick MWCNTs (CNTLarge, 4 +/- 0.4 mu m long). Liver tissues and plasma were harvested 1,3 and 28 days 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. (C) 2015 The Authors. Published by Elsevier Inc.",
keywords = "Nanotoxicology, Atherosclerosis, Toxicogenomics, Liver, Acute phase response, Histology",
author = "Poulsen, {Sarah S.} and Saber, {Anne T.} and Alicja Mortensen and Jozef Szarek and Dongmei Wu and Andrew Williams and Ole Andersen and Jacobsen, {Nicklas R.} and Yauk, {Carole L.} and Hakan Wallin and Sabina Halappanavar and Vogel, {Ulla Birgitte}",
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Poulsen, SS, Saber, AT, Mortensen, A, Szarek, J, Wu, D, Williams, A, Andersen, O, Jacobsen, NR, Yauk, CL, Wallin, H, Halappanavar, S & Vogel, UB 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, vol. 283, no. 3, pp. 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; Szarek, Jozef; Wu, Dongmei; Williams, Andrew; Andersen, Ole; Jacobsen, Nicklas R.; Yauk, Carole L.; Wallin, Hakan; Halappanavar, Sabina; Vogel, Ulla Birgitte.

In: Toxicology and Applied Pharmacology, Vol. 283, No. 3, 2015, p. 210-222.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

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, Jozef

AU - Wu, Dongmei

AU - Williams, Andrew

AU - Andersen, Ole

AU - Jacobsen, Nicklas R.

AU - Yauk, Carole L.

AU - Wallin, Hakan

AU - Halappanavar, Sabina

AU - Vogel, Ulla Birgitte

N1 - © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

PY - 2015

Y1 - 2015

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 162 mu g/mouse of small, entangled (CNTsmall, 0.8 +/- 0.1 pm long) or large, thick MWCNTs (CNTLarge, 4 +/- 0.4 mu m long). Liver tissues and plasma were harvested 1,3 and 28 days 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. (C) 2015 The Authors. Published by Elsevier Inc.

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 162 mu g/mouse of small, entangled (CNTsmall, 0.8 +/- 0.1 pm long) or large, thick MWCNTs (CNTLarge, 4 +/- 0.4 mu m long). Liver tissues and plasma were harvested 1,3 and 28 days 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. (C) 2015 The Authors. Published by Elsevier Inc.

KW - Nanotoxicology

KW - Atherosclerosis

KW - Toxicogenomics

KW - Liver

KW - Acute phase response

KW - Histology

U2 - 10.1016/j.taap.2015.01.011

DO - 10.1016/j.taap.2015.01.011

M3 - Journal article

C2 - 25620056

VL - 283

SP - 210

EP - 222

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 3

ER -