Angiogene Faktoren und ihre Rolle in der Entstehung und Vorhersage der Präeklampsie

Zusammenfassung

Obwohl die Ätiologie der Präeklampsie noch immer nicht vollständig geklärt werden konnte, gibt es mittlerweile überzeugende Hinweise dafür, dass eine Dysbalance zwischen angiogenen Faktoren wie placental growth factor (PlGF) und anti-angiogenen Faktoren wie soluble fms-like tyrosine kinase 1 (sFlt1) und soluble Endoglin (sENG) ein zentrales pathogenetisches Ereignis bei der Entstehung der Präeklampsie ist. Durch die Erforschung angiogener Faktoren scheint man, wenn nicht der Ursache der Präeklampsie, so doch den entscheidenden pathogenetischen Mediatoren sehr nahe gekommen zu sein. Da antiangiogene Faktoren wie sFlt1 und sENG bereits Wochen vor Manifestation einer Präeklampsie sehr stark erhöht im mütterlichen Blut messbar sind und maternale Serumkonzentrationen dieser Faktoren gut mit dem klinischen Verlauf korrelieren, ist jetzt im Risikokollektiv eine sehr gute klinische Prognose möglich. Im Risikokollektiv von Schwangeren mit uteriner Perfusionsstörung im 2. Trimenon hat der Doppler allein nur eine Spezifität von 60% bzw. eine positive Vorhersage von 58% bezüglich aller später auftretender Komplikationen (PE+IUGR). Die parallele Messung von sFlt1 und PlGF kann die Erkennung einer early-onset-Präeklampsie (<34. SSW) auf 83% Sensitivität, 95% Spezifität und 71% positive Vorhersage deutlich verbessern. Bei kombinierter Messung von uterinem Doppler, sENG und sFlt1 betrug die Sensitivität hinsichtlich early-onset-Präeklampsie sogar 99% und die Spezifität 93%. Der nächste Schritt wird die Entwicklung einer theoretisch möglichen therapeutischen Intervention sein, die durch die Beeinflussung des angiogenen-anti-angiogenen Gleichgewichts die präeklamptischen Symptome positiv beeinflussen kann.

Abstract

Angiogenic factors like placental growth factor (PlGF) and its anti-angiogenic antagonists soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) are closely related to the pathogenesis of preeclampsia and intrauterine growth restriction (IUGR). The discovery and investigation of these angiogenic factors could characterize important pathogenetic mediators of preeclampsia or even the cause for placental dysfunctions. These anti-angiogenic proteins are dramatically elevated in maternal circulation weeks prior to the onset of the syndrome preeclampsia. Since it is known that altered maternal sFlt1, sEng and PlGF levels are detectable weeks prior to the onset of these pregnancy complications, it was the aim of the study to investigate the predictive value of these markers in high-risk second trimester pregnancies characterized by abnormal uterine perfusion. Using both factors, sFlt1 and PlGF, early-onset preeclampsia can be predicted with 83% sensitivity and 95% specificity. Combined analysis of sEng and sFlt1 is able to predict early-onset PE even with a sensitivity of 100% and a specificity of 93.3%. This shows, that the concurrent measurement of uterine perfusion and angiogenic factors allows an efficient prediction of early-onset pregnancy complications, particularly preeclampsia. The next step will be the development of therapeutic tools that have positive impact on the clinical symptoms via the inhibition of sFlt1 and or sEng.

Schlüsselwörter

Präeklampsie - angiogene Fraktoren - Prädiktion - PLGF - sFlt 1 - sEng

Key words

preeclampsia - angiogenic factors - predictive value - PlGF - sFlt 1 - sEng

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