Lps-induced systemic inflammation does not alter atherosclerotic plaque area or inflammation in ApoE3*Leiden mice in the early phase up to 15 days

Wessel W. Fuijkschot, Martine C. Morrison, Ilse P. A. Zethof, Paul A. J. Krijnen, Robert Kleemann, Hans W. M. Niessen, Yvo M. Smulders

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background and Aims: Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intraplaque inflammation. We evaluated whether lipopolysaccharides (LPS)-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions. Methods and Results: ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis. Thereafter, mice received a single intraperitoneal injection with LPS to induce systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days post-LPS injection (n ¼ 17) or post-saline injection (n ¼ 13). Serum amyloid A, a sensitive marker of systemic inflammation, increased 250-fold in LPS-treated mice. Aortic root plaques were assessed for total plaque area, plaque severity, and inflammatory cell content. No significant differences in total surface area of atherosclerotic plaque were found between control and LPS groups sacrificed after 2 days (resp. 0.409 0.228 105 mm2 vs. 0.285 0.169 105 mm2) (P ¼ 0.31), and 15 days (resp. 0.950 0.938 105 mm2 vs. 0.612 0.413 105 mm2) (P ¼ 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the groups. Conclusions: Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.
Original languageEnglish
Pages (from-to)360-365
JournalShock
Volume50
Issue number3
Early online date11 Oct 2017
DOIs
Publication statusPublished - 2018

Cite this

@article{2525ff3dfe16452c9c7845ced9386f6b,
title = "Lps-induced systemic inflammation does not alter atherosclerotic plaque area or inflammation in ApoE3*Leiden mice in the early phase up to 15 days",
abstract = "Background and Aims: Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intraplaque inflammation. We evaluated whether lipopolysaccharides (LPS)-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions. Methods and Results: ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis. Thereafter, mice received a single intraperitoneal injection with LPS to induce systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days post-LPS injection (n ¼ 17) or post-saline injection (n ¼ 13). Serum amyloid A, a sensitive marker of systemic inflammation, increased 250-fold in LPS-treated mice. Aortic root plaques were assessed for total plaque area, plaque severity, and inflammatory cell content. No significant differences in total surface area of atherosclerotic plaque were found between control and LPS groups sacrificed after 2 days (resp. 0.409 0.228 105 mm2 vs. 0.285 0.169 105 mm2) (P ¼ 0.31), and 15 days (resp. 0.950 0.938 105 mm2 vs. 0.612 0.413 105 mm2) (P ¼ 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the groups. Conclusions: Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.",
keywords = "Journal Article",
author = "Fuijkschot, {Wessel W.} and Morrison, {Martine C.} and Zethof, {Ilse P. A.} and Krijnen, {Paul A. J.} and Robert Kleemann and Niessen, {Hans W. M.} and Smulders, {Yvo M.}",
year = "2018",
doi = "10.1097/SHK.0000000000001026",
language = "English",
volume = "50",
pages = "360--365",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "3",

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Lps-induced systemic inflammation does not alter atherosclerotic plaque area or inflammation in ApoE3*Leiden mice in the early phase up to 15 days. / Fuijkschot, Wessel W.; Morrison, Martine C.; Zethof, Ilse P. A.; Krijnen, Paul A. J.; Kleemann, Robert; Niessen, Hans W. M.; Smulders, Yvo M.

In: Shock, Vol. 50, No. 3, 2018, p. 360-365.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Lps-induced systemic inflammation does not alter atherosclerotic plaque area or inflammation in ApoE3*Leiden mice in the early phase up to 15 days

AU - Fuijkschot, Wessel W.

AU - Morrison, Martine C.

AU - Zethof, Ilse P. A.

AU - Krijnen, Paul A. J.

AU - Kleemann, Robert

AU - Niessen, Hans W. M.

AU - Smulders, Yvo M.

PY - 2018

Y1 - 2018

N2 - Background and Aims: Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intraplaque inflammation. We evaluated whether lipopolysaccharides (LPS)-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions. Methods and Results: ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis. Thereafter, mice received a single intraperitoneal injection with LPS to induce systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days post-LPS injection (n ¼ 17) or post-saline injection (n ¼ 13). Serum amyloid A, a sensitive marker of systemic inflammation, increased 250-fold in LPS-treated mice. Aortic root plaques were assessed for total plaque area, plaque severity, and inflammatory cell content. No significant differences in total surface area of atherosclerotic plaque were found between control and LPS groups sacrificed after 2 days (resp. 0.409 0.228 105 mm2 vs. 0.285 0.169 105 mm2) (P ¼ 0.31), and 15 days (resp. 0.950 0.938 105 mm2 vs. 0.612 0.413 105 mm2) (P ¼ 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the groups. Conclusions: Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.

AB - Background and Aims: Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intraplaque inflammation. We evaluated whether lipopolysaccharides (LPS)-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions. Methods and Results: ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis. Thereafter, mice received a single intraperitoneal injection with LPS to induce systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days post-LPS injection (n ¼ 17) or post-saline injection (n ¼ 13). Serum amyloid A, a sensitive marker of systemic inflammation, increased 250-fold in LPS-treated mice. Aortic root plaques were assessed for total plaque area, plaque severity, and inflammatory cell content. No significant differences in total surface area of atherosclerotic plaque were found between control and LPS groups sacrificed after 2 days (resp. 0.409 0.228 105 mm2 vs. 0.285 0.169 105 mm2) (P ¼ 0.31), and 15 days (resp. 0.950 0.938 105 mm2 vs. 0.612 0.413 105 mm2) (P ¼ 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the groups. Conclusions: Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.

KW - Journal Article

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UR - https://www.ncbi.nlm.nih.gov/pubmed/29023363

U2 - 10.1097/SHK.0000000000001026

DO - 10.1097/SHK.0000000000001026

M3 - Article

VL - 50

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EP - 365

JO - Shock

JF - Shock

SN - 1073-2322

IS - 3

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