Statins promote cardiac infarct healing by modulating endothelial barrier function revealed by contrast-enhanced magnetic resonance imaging

G.J. Leenders, M.B. Smeets, M. Van Den Boomen, M. Berben, M. Nabben, D. Van Strijp, G.J. Strijkers, J.J. Prompers, F. Arslan, K. Nicolay, K. Vandoorne

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Objective - The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI). Approach and Results - Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE -/-, and statin-treated ApoE -/- mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE -/- infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE -/- infarcts, indicated by reduced permeability. The infarcted tissue of ApoE -/- mice 3 days post-MI displayed an unbalanced Vegfa(vascular endothelial growth factor A)/Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45 + leukocytes and inflammatory LY6C hi monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE -/- mice. Conclusions - Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.

Original languageEnglish
Pages (from-to)186-194
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Apolipoproteins E
Magnetic Resonance Imaging
Myocardial Infarction
Permeability
Leukocytes
Vascular Endothelial Growth Factor A
Capillary Permeability
Wound Healing
Endothelium
Blood Vessels
Dilatation
Monocytes
Atherosclerosis
Histology
Flow Cytometry
Lipids
Polymerase Chain Reaction

Keywords

  • atherosclerosis
  • hydroxymethylglutaryl-CoA reductase inhibitors
  • magnetic resonance imaging
  • myocardial infarction
  • permeability

Cite this

Leenders, G.J. ; Smeets, M.B. ; Van Den Boomen, M. ; Berben, M. ; Nabben, M. ; Van Strijp, D. ; Strijkers, G.J. ; Prompers, J.J. ; Arslan, F. ; Nicolay, K. ; Vandoorne, K. / Statins promote cardiac infarct healing by modulating endothelial barrier function revealed by contrast-enhanced magnetic resonance imaging. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2018 ; Vol. 38, No. 1. pp. 186-194.
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abstract = "Objective - The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI). Approach and Results - Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE -/-, and statin-treated ApoE -/- mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE -/- infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE -/- infarcts, indicated by reduced permeability. The infarcted tissue of ApoE -/- mice 3 days post-MI displayed an unbalanced Vegfa(vascular endothelial growth factor A)/Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45 + leukocytes and inflammatory LY6C hi monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE -/- mice. Conclusions - Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.",
keywords = "atherosclerosis, hydroxymethylglutaryl-CoA reductase inhibitors, magnetic resonance imaging, myocardial infarction, permeability",
author = "G.J. Leenders and M.B. Smeets and {Van Den Boomen}, M. and M. Berben and M. Nabben and {Van Strijp}, D. and G.J. Strijkers and J.J. Prompers and F. Arslan and K. Nicolay and K. Vandoorne",
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Statins promote cardiac infarct healing by modulating endothelial barrier function revealed by contrast-enhanced magnetic resonance imaging. / Leenders, G.J.; Smeets, M.B.; Van Den Boomen, M.; Berben, M.; Nabben, M.; Van Strijp, D.; Strijkers, G.J.; Prompers, J.J.; Arslan, F.; Nicolay, K.; Vandoorne, K.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 38, No. 1, 01.01.2018, p. 186-194.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Statins promote cardiac infarct healing by modulating endothelial barrier function revealed by contrast-enhanced magnetic resonance imaging

AU - Leenders, G.J.

AU - Smeets, M.B.

AU - Van Den Boomen, M.

AU - Berben, M.

AU - Nabben, M.

AU - Van Strijp, D.

AU - Strijkers, G.J.

AU - Prompers, J.J.

AU - Arslan, F.

AU - Nicolay, K.

AU - Vandoorne, K.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective - The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI). Approach and Results - Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE -/-, and statin-treated ApoE -/- mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE -/- infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE -/- infarcts, indicated by reduced permeability. The infarcted tissue of ApoE -/- mice 3 days post-MI displayed an unbalanced Vegfa(vascular endothelial growth factor A)/Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45 + leukocytes and inflammatory LY6C hi monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE -/- mice. Conclusions - Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.

AB - Objective - The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at the inflammatory (day 3) and the reparative (day 7) phase of infarct healing post-MI using contrast-enhanced cardiac magnetic resonance imaging (MRI). Approach and Results - Noninvasive permeability mapping by MRI after MI in C57BL/6, atherosclerotic ApoE -/-, and statin-treated ApoE -/- mice was correlated to subsequent left ventricular outcome by structural and functional cardiac MRI. Ex vivo histology, flow cytometry, and quantitative polymerase chain reaction were performed on infarct regions. Increased vascular permeability at ApoE -/- infarcts was observed compared with C57BL/6 infarcts, predicting enhanced left ventricular dilation at day 21 post-MI by MRI volumetry. Statin treatment improved vascular barrier function at ApoE -/- infarcts, indicated by reduced permeability. The infarcted tissue of ApoE -/- mice 3 days post-MI displayed an unbalanced Vegfa(vascular endothelial growth factor A)/Angpt1 (angiopoetin-1) expression ratio (explaining leakage-prone vessels), associated with higher amounts of CD45 + leukocytes and inflammatory LY6C hi monocytes. Statins reversed the unbalanced Vegfa/Angpt1 expression, normalizing endothelial barrier function at the infarct and blocking the augmented recruitment of inflammatory leukocytes in statin-treated ApoE -/- mice. Conclusions - Statins lowered permeability and reduced the transit of unfavorable inflammatory leukocytes into the infarcted tissue, consequently improving left ventricular outcome.

KW - atherosclerosis

KW - hydroxymethylglutaryl-CoA reductase inhibitors

KW - magnetic resonance imaging

KW - myocardial infarction

KW - permeability

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U2 - 10.1161/ATVBAHA.117.310339

DO - 10.1161/ATVBAHA.117.310339

M3 - Article

C2 - 29146749

AN - SCOPUS:85039419497

VL - 38

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EP - 194

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

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