Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction
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Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction. / Savvatis, Konstantinos; Pappritz, Kathleen; Becher, Peter Moritz; Lindner, Diana; Zietsch, Christin; Volk, Hans-Dieter; Westermann, Dirk; Schultheiss, Heinz-Peter; Tschöpe, Carsten.
in: CIRC-HEART FAIL, Jahrgang 7, Nr. 1, 01.2014, S. 161-171.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction
AU - Savvatis, Konstantinos
AU - Pappritz, Kathleen
AU - Becher, Peter Moritz
AU - Lindner, Diana
AU - Zietsch, Christin
AU - Volk, Hans-Dieter
AU - Westermann, Dirk
AU - Schultheiss, Heinz-Peter
AU - Tschöpe, Carsten
PY - 2014/1
Y1 - 2014/1
N2 - BACKGROUND: CD4+ cells are implicated in the healing process after myocardial infarction (MI). We sought to investigate the role of interleukin-23 (IL-23) deficiency, a cytokine important in differentiation of CD4+ cells, in scar formation of the ischemic heart.METHODS AND RESULTS: MI was performed in wild-type and IL23p19-/- mice. Thirty-day mortality, hemodynamic function 4 days after MI and myocardial inflammation, and remodeling 4 and 30 days after MI were examined. Differentiation of fibroblasts from infarcted and noninfarcted hearts into myofibroblasts was examined under basal conditions and after stimulation with interferon-γ, IL-17α and IL-23. Interleukin-23p19-/- mice showed higher expression of proinflammatory cytokines and immune cell infiltration in the scar early after MI compared with wild-type mice. A stronger interferon-γ/Th1 reaction seemed to be responsible for the increased inflammation under IL-23 deficiency. Expression of α-smooth muscle actin (α-SMA), collagen I and III was significantly higher in the heart tissue and isolated cardiac fibroblasts 4 days after MI in the wild-type mice. Interleukin-23p19-/- mice showed impaired healing compared with wild-type mice, as seen by significantly higher mortality because of ventricular rupture (40% higher after 30 days) and stronger left ventricular dilation early after MI. Stimulation of cardiac fibroblasts with interferon-γ, the main Th1 cytokine, but not with IL-23 or IL-17α, led to a significant downregulation of α-smooth muscle actin, collagen I and III and decreased migration and differentiation to myofibroblasts.CONCLUSIONS: IL-23 deficiency leads to increased myocardial inflammation and decreased cardiac fibroblast activation, associated with impaired scar formation and adverse remodeling after MI.
AB - BACKGROUND: CD4+ cells are implicated in the healing process after myocardial infarction (MI). We sought to investigate the role of interleukin-23 (IL-23) deficiency, a cytokine important in differentiation of CD4+ cells, in scar formation of the ischemic heart.METHODS AND RESULTS: MI was performed in wild-type and IL23p19-/- mice. Thirty-day mortality, hemodynamic function 4 days after MI and myocardial inflammation, and remodeling 4 and 30 days after MI were examined. Differentiation of fibroblasts from infarcted and noninfarcted hearts into myofibroblasts was examined under basal conditions and after stimulation with interferon-γ, IL-17α and IL-23. Interleukin-23p19-/- mice showed higher expression of proinflammatory cytokines and immune cell infiltration in the scar early after MI compared with wild-type mice. A stronger interferon-γ/Th1 reaction seemed to be responsible for the increased inflammation under IL-23 deficiency. Expression of α-smooth muscle actin (α-SMA), collagen I and III was significantly higher in the heart tissue and isolated cardiac fibroblasts 4 days after MI in the wild-type mice. Interleukin-23p19-/- mice showed impaired healing compared with wild-type mice, as seen by significantly higher mortality because of ventricular rupture (40% higher after 30 days) and stronger left ventricular dilation early after MI. Stimulation of cardiac fibroblasts with interferon-γ, the main Th1 cytokine, but not with IL-23 or IL-17α, led to a significant downregulation of α-smooth muscle actin, collagen I and III and decreased migration and differentiation to myofibroblasts.CONCLUSIONS: IL-23 deficiency leads to increased myocardial inflammation and decreased cardiac fibroblast activation, associated with impaired scar formation and adverse remodeling after MI.
KW - Animals
KW - Cell Differentiation/drug effects
KW - Cell Movement/drug effects
KW - Cells, Cultured
KW - Cicatrix/pathology
KW - Cytokines/metabolism
KW - Disease Models, Animal
KW - Fibroblasts/drug effects
KW - Interferon-gamma/pharmacology
KW - Interleukin-17/pharmacology
KW - Interleukin-23/deficiency
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Myocardial Infarction/diagnosis
KW - Prognosis
KW - Wound Healing/physiology
U2 - 10.1161/CIRCHEARTFAILURE.113.000604
DO - 10.1161/CIRCHEARTFAILURE.113.000604
M3 - SCORING: Journal article
C2 - 24300243
VL - 7
SP - 161
EP - 171
JO - CIRC-HEART FAIL
JF - CIRC-HEART FAIL
SN - 1941-3289
IS - 1
ER -
