Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice

Amber van Broekhoven, Paul A.J. Krijnen, Wessel W. Fuijkschot, Martine C. Morrison, Ilse P.A. Zethof, Wessel N. van Wieringen, Yvo M. Smulders, Hans W.M. Niessen, Alexander B.A. Vonk

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: Recently, it was shown that 12 weeks of lipopolysaccharide (LPS) administration to nonatherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short-term effect of LPS on the AVs in an atherosclerotic mouse model. Methods: ApoE*3Leiden mice, on an atherogenic diet, were injected intraperitoneally with either LPS or phosphate buffered saline (PBS), and sacrificed 2 or 15 days later. AVs were assessed for size, fibrosis, glycosaminoglycans (GAGs), lipids, calcium deposits, iron deposits and inflammatory cells. Results: LPS injection caused an increase in maximal leaflet thickness at 2 days (128.4 µm) compared to PBS-injected mice (67.8 µm; P = 0.007), whereas at 15 days this was not significantly different. LPS injection did not significantly affect average AV thickness on day 2 (37.8 µm), but did significantly increase average AV thickness at day 15 (41.6 µm; P = 0.038) compared to PBS-injected mice (31.7 and 32.3 µm respectively). LPS injection did not affect AV fibrosis, GAGs and lipid content. Furthermore, no calcium deposits were found. Iron deposits, indicative for valve haemorrhage, were observed in one AV of the PBS-injected group (a day 2 mouse; 9.1%) and in five AVs of the LPS-injected group (both day 2- and 15 mice; 29.4%). No significant differences in inflammatory cell infiltration were observed upon LPS injection. Conclusion: Short-term LPS apparently has the potential to increase AV thickening and haemorrhage. These results suggest that systemic inflammation can acutely compromise AV structure.

Original languageEnglish
Article numbere13121
Pages (from-to)1-10
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume49
Issue number7
Early online date23 Apr 2019
DOIs
Publication statusPublished - 1 Jul 2019

Fingerprint

Apolipoproteins E
Aortic Valve
Heart Valves
Lipopolysaccharides
Iron deposits
Phosphates
Injections
Glycosaminoglycans
Fibrosis
Iron
Atherogenic Diet
Hemorrhage
Calcium
Lipids
Aortic Valve Stenosis
Nutrition
Infiltration
Atherosclerosis
Inflammation

Keywords

  • animal model
  • aortic valve stenosis
  • atherosclerosis
  • lipopolysaccharide
  • systemic inflammation

Cite this

van Broekhoven, A., Krijnen, P. A. J., Fuijkschot, W. W., Morrison, M. C., Zethof, I. P. A., van Wieringen, W. N., ... Vonk, A. B. A. (2019). Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice. European Journal of Clinical Investigation, 49(7), 1-10. [e13121]. https://doi.org/10.1111/eci.13121
van Broekhoven, Amber ; Krijnen, Paul A.J. ; Fuijkschot, Wessel W. ; Morrison, Martine C. ; Zethof, Ilse P.A. ; van Wieringen, Wessel N. ; Smulders, Yvo M. ; Niessen, Hans W.M. ; Vonk, Alexander B.A. / Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice. In: European Journal of Clinical Investigation. 2019 ; Vol. 49, No. 7. pp. 1-10.
@article{8aec0e8958f048daab532bb162d3fd61,
title = "Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice",
abstract = "Background: Recently, it was shown that 12 weeks of lipopolysaccharide (LPS) administration to nonatherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short-term effect of LPS on the AVs in an atherosclerotic mouse model. Methods: ApoE*3Leiden mice, on an atherogenic diet, were injected intraperitoneally with either LPS or phosphate buffered saline (PBS), and sacrificed 2 or 15 days later. AVs were assessed for size, fibrosis, glycosaminoglycans (GAGs), lipids, calcium deposits, iron deposits and inflammatory cells. Results: LPS injection caused an increase in maximal leaflet thickness at 2 days (128.4 µm) compared to PBS-injected mice (67.8 µm; P = 0.007), whereas at 15 days this was not significantly different. LPS injection did not significantly affect average AV thickness on day 2 (37.8 µm), but did significantly increase average AV thickness at day 15 (41.6 µm; P = 0.038) compared to PBS-injected mice (31.7 and 32.3 µm respectively). LPS injection did not affect AV fibrosis, GAGs and lipid content. Furthermore, no calcium deposits were found. Iron deposits, indicative for valve haemorrhage, were observed in one AV of the PBS-injected group (a day 2 mouse; 9.1{\%}) and in five AVs of the LPS-injected group (both day 2- and 15 mice; 29.4{\%}). No significant differences in inflammatory cell infiltration were observed upon LPS injection. Conclusion: Short-term LPS apparently has the potential to increase AV thickening and haemorrhage. These results suggest that systemic inflammation can acutely compromise AV structure.",
keywords = "animal model, aortic valve stenosis, atherosclerosis, lipopolysaccharide, systemic inflammation",
author = "{van Broekhoven}, Amber and Krijnen, {Paul A.J.} and Fuijkschot, {Wessel W.} and Morrison, {Martine C.} and Zethof, {Ilse P.A.} and {van Wieringen}, {Wessel N.} and Smulders, {Yvo M.} and Niessen, {Hans W.M.} and Vonk, {Alexander B.A.}",
year = "2019",
month = "7",
day = "1",
doi = "10.1111/eci.13121",
language = "English",
volume = "49",
pages = "1--10",
journal = "European Journal of Clinical Investigation",
issn = "0014-2972",
publisher = "Wiley-Blackwell Publishing",
number = "7",

}

van Broekhoven, A, Krijnen, PAJ, Fuijkschot, WW, Morrison, MC, Zethof, IPA, van Wieringen, WN, Smulders, YM, Niessen, HWM & Vonk, ABA 2019, 'Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice' European Journal of Clinical Investigation, vol. 49, no. 7, e13121, pp. 1-10. https://doi.org/10.1111/eci.13121

Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice. / van Broekhoven, Amber; Krijnen, Paul A.J.; Fuijkschot, Wessel W.; Morrison, Martine C.; Zethof, Ilse P.A.; van Wieringen, Wessel N.; Smulders, Yvo M.; Niessen, Hans W.M.; Vonk, Alexander B.A.

In: European Journal of Clinical Investigation, Vol. 49, No. 7, e13121, 01.07.2019, p. 1-10.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice

AU - van Broekhoven, Amber

AU - Krijnen, Paul A.J.

AU - Fuijkschot, Wessel W.

AU - Morrison, Martine C.

AU - Zethof, Ilse P.A.

AU - van Wieringen, Wessel N.

AU - Smulders, Yvo M.

AU - Niessen, Hans W.M.

AU - Vonk, Alexander B.A.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background: Recently, it was shown that 12 weeks of lipopolysaccharide (LPS) administration to nonatherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short-term effect of LPS on the AVs in an atherosclerotic mouse model. Methods: ApoE*3Leiden mice, on an atherogenic diet, were injected intraperitoneally with either LPS or phosphate buffered saline (PBS), and sacrificed 2 or 15 days later. AVs were assessed for size, fibrosis, glycosaminoglycans (GAGs), lipids, calcium deposits, iron deposits and inflammatory cells. Results: LPS injection caused an increase in maximal leaflet thickness at 2 days (128.4 µm) compared to PBS-injected mice (67.8 µm; P = 0.007), whereas at 15 days this was not significantly different. LPS injection did not significantly affect average AV thickness on day 2 (37.8 µm), but did significantly increase average AV thickness at day 15 (41.6 µm; P = 0.038) compared to PBS-injected mice (31.7 and 32.3 µm respectively). LPS injection did not affect AV fibrosis, GAGs and lipid content. Furthermore, no calcium deposits were found. Iron deposits, indicative for valve haemorrhage, were observed in one AV of the PBS-injected group (a day 2 mouse; 9.1%) and in five AVs of the LPS-injected group (both day 2- and 15 mice; 29.4%). No significant differences in inflammatory cell infiltration were observed upon LPS injection. Conclusion: Short-term LPS apparently has the potential to increase AV thickening and haemorrhage. These results suggest that systemic inflammation can acutely compromise AV structure.

AB - Background: Recently, it was shown that 12 weeks of lipopolysaccharide (LPS) administration to nonatherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short-term effect of LPS on the AVs in an atherosclerotic mouse model. Methods: ApoE*3Leiden mice, on an atherogenic diet, were injected intraperitoneally with either LPS or phosphate buffered saline (PBS), and sacrificed 2 or 15 days later. AVs were assessed for size, fibrosis, glycosaminoglycans (GAGs), lipids, calcium deposits, iron deposits and inflammatory cells. Results: LPS injection caused an increase in maximal leaflet thickness at 2 days (128.4 µm) compared to PBS-injected mice (67.8 µm; P = 0.007), whereas at 15 days this was not significantly different. LPS injection did not significantly affect average AV thickness on day 2 (37.8 µm), but did significantly increase average AV thickness at day 15 (41.6 µm; P = 0.038) compared to PBS-injected mice (31.7 and 32.3 µm respectively). LPS injection did not affect AV fibrosis, GAGs and lipid content. Furthermore, no calcium deposits were found. Iron deposits, indicative for valve haemorrhage, were observed in one AV of the PBS-injected group (a day 2 mouse; 9.1%) and in five AVs of the LPS-injected group (both day 2- and 15 mice; 29.4%). No significant differences in inflammatory cell infiltration were observed upon LPS injection. Conclusion: Short-term LPS apparently has the potential to increase AV thickening and haemorrhage. These results suggest that systemic inflammation can acutely compromise AV structure.

KW - animal model

KW - aortic valve stenosis

KW - atherosclerosis

KW - lipopolysaccharide

KW - systemic inflammation

UR - http://www.scopus.com/inward/record.url?scp=85066023158&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066023158&partnerID=8YFLogxK

U2 - 10.1111/eci.13121

DO - 10.1111/eci.13121

M3 - Article

VL - 49

SP - 1

EP - 10

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

IS - 7

M1 - e13121

ER -

van Broekhoven A, Krijnen PAJ, Fuijkschot WW, Morrison MC, Zethof IPA, van Wieringen WN et al. Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice. European Journal of Clinical Investigation. 2019 Jul 1;49(7):1-10. e13121. https://doi.org/10.1111/eci.13121