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Die Charakterisierung des akuten ST-Hebungsinfarkts durch die kontrastverstärkte Magnetresonanztomographie liefert signifikante, inkrementelle, prognostische Information über die klinische Risikoevaluation hinaus. Die Größe der mikrovaskulären Obstruktion, hat unter den MRT Parametern den besten prognostischen Wert und ist ein inkrementeller Prädiktor von kardiovaskulären Ereignissen. Die Ergebnisse dieser Studie könnten im klinischen Alltag relevant werden, wenn es darum geht Patienten herauszufiltern, die von einer strikten medikamentösen Therapie, zur Vorbeugung eines linksventrikulären Remodellings und zur Unterstützung der Reparaturvorgänge im infarzierten Myokard, profitieren würden. Der prädiktive Wert der MVO in der kontrastverstärkten MRT ist mit der in der Tc99m-sestamibi SPECT bestimmten Infarktgröße vergleichbar und könnte diese Modalität in der Risikoevaluation bei Patienten nach Reperfusion im akutem Myokardinfarkt ersetzen., The characterisation of acute ST-elevation myocardial infarction by contrast-enhanced magnetic resonance imaging is an incremental predictor of adverse cardiac events and may be useful in the risk stratification of survivors of acute myocardial infarction. The size of microvascular obstruction has the best prognostic value of all MRI parameters and is an incremental predictor of adverse cardiac events. In the clinical setting, the findings of this study may become relevant, when there is a need for selection of patients who may benefit from most stringent medical therapy to prevent adverse remodeling and to facilitate the repair of infarcted myocardium. The predictive value of MVO assessed by MRI is comparable to infarct size assessment by Tc99m-sestamibi SPECT and might replace this modality for risk assessment of patients after reperfusion in acute myocardial infarction.

Die Charakterisierung des akuten ST-Hebungsinfarkts durch die kontrastverstärkte Magnetresonanztomographie liefert signifikante, inkrementelle, prognostische Information über die klinische Risikoevaluation hinaus. Die Größe der mikrovaskulären Obstruktion, hat unter den MRT Parametern den besten prognostischen Wert und ist ein inkrementeller Prädiktor von kardiovaskulären Ereignissen. Die Ergebnisse dieser Studie könnten im klinischen Alltag relevant werden, wenn es darum geht Patienten herauszufiltern, die von einer strikten medikamentösen Therapie, zur Vorbeugung eines linksventrikulären Remodellings und zur Unterstützung der Reparaturvorgänge im infarzierten Myokard, profitieren würden. Der prädiktive Wert der MVO in der kontrastverstärkten MRT ist mit der in der Tc99m-sestamibi SPECT bestimmten Infarktgröße vergleichbar und könnte diese Modalität in der Risikoevaluation bei Patienten nach Reperfusion im akutem Myokardinfarkt ersetzen., The characterisation of acute ST-elevation myocardial infarction by contrast-enhanced magnetic resonance imaging is an incremental predictor of adverse cardiac events and may be useful in the risk stratification of survivors of acute myocardial infarction. The size of microvascular obstruction has the best prognostic value of all MRI parameters and is an incremental predictor of adverse cardiac events. In the clinical setting, the findings of this study may become relevant, when there is a need for selection of patients who may benefit from most stringent medical therapy to prevent adverse remodeling and to facilitate the repair of infarcted myocardium. The predictive value of MVO assessed by MRI is comparable to infarct size assessment by Tc99m-sestamibi SPECT and might replace this modality for risk assessment of patients after reperfusion in acute myocardial infarction.

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-beta/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t). We identify the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) as a key negative regulator of human and mouse Th17 differentiation. PPAR gamma activation in CD4(+) T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentiation by PPAR gamma involved inhibition of TGF-beta/IL-6-induced expression of ROR gamma t in T cells. Pharmacologic activation of PPAR gamma prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the ROR gamma t promoter in T cells, thus interfering with ROR gamma t transcription. Both T cell-specific PPAR gamma knockout and endogenous ligand activation revealed the physiological role of PPAR gamma for continuous T cell-intrinsic control of Th17 differentiation and development of autoimmunity. Importantly, human CD4(+) T cells from healthy controls and MS patients were strongly susceptible to PPAR gamma-mediated suppression of Th17 differentiation. In summary, we report a PPAR gamma-mediated T cell-intrinsic molecular mechanism that selectively controls Th17 differentiation in mice and in humans and that is amenable to pharmacologic modulation. We therefore propose that PPAR gamma represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as MS.

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-beta/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t). We identify the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) as a key negative regulator of human and mouse Th17 differentiation. PPAR gamma activation in CD4(+) T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentiation by PPAR gamma involved inhibition of TGF-beta/IL-6-induced expression of ROR gamma t in T cells. Pharmacologic activation of PPAR gamma prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the ROR gamma t promoter in T cells, thus interfering with ROR gamma t transcription. Both T cell-specific PPAR gamma knockout and endogenous ligand activation revealed the physiological role of PPAR gamma for continuous T cell-intrinsic control of Th17 differentiation and development of autoimmunity. Importantly, human CD4(+) T cells from healthy controls and MS patients were strongly susceptible to PPAR gamma-mediated suppression of Th17 differentiation. In summary, we report a PPAR gamma-mediated T cell-intrinsic molecular mechanism that selectively controls Th17 differentiation in mice and in humans and that is amenable to pharmacologic modulation. We therefore propose that PPAR gamma represents a promising molecular target for specific immunointervention in Th17-mediated autoimmune diseases such as MS.