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

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4 Citaties (Scopus)

Uittreksel

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.

TaalEngels
Pagina's186-194
Aantal pagina's9
TijdschriftArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 1 jan 2018

Vingerafdruk

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

Trefwoorden

    Citeer dit

    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, Nr. 1. blz. 186-194
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    title = "Statins promote cardiac infarct healing by modulating endothelial barrier function revealed by contrast-enhanced magnetic resonance imaging",
    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",
    year = "2018",
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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, Nr. 1, 01.01.2018, blz. 186-194.

    Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer 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

    UR - http://www.scopus.com/inward/record.url?scp=85039419497&partnerID=8YFLogxK

    U2 - 10.1161/ATVBAHA.117.310339

    DO - 10.1161/ATVBAHA.117.310339

    M3 - Article

    VL - 38

    SP - 186

    EP - 194

    JO - Arteriosclerosis, Thrombosis, and Vascular Biology

    T2 - Arteriosclerosis, Thrombosis, and Vascular Biology

    JF - Arteriosclerosis, Thrombosis, and Vascular Biology

    SN - 1079-5642

    IS - 1

    ER -