Die pulmonal arterielle Hypertonie (PAH) ist eine seltene Erkrankung, charakterisiert durch einen Gefäßumbau von kleinen Lungenarterien, der zu einer Verringerung des Lumens bis hin zur Okklusion führt. Nach den aktuellen Leitlinien wird eine PAH durch einen pulmonal arteriellen Druck ≥ 25 mmHg, durch einen arteriellen Wedgedruck ≤ 15 mmHg und durch einen erhöhten pulmonal vaskulären Widerstand (PVR > 3 WU) definiert. Die aktuellen pathophysiologischen Konzepte über die Entstehung der Krankheit schließen Störungen in der Produktion, Deposition und Komposition von Faktoren der extrazellulären Matrix, Entzündungsprozesse, Mutationen im BMPR2-Gen und Mutationen im KCNK3-Gen mit ein. In den letzten Jahren brachten epigenetische und genetische Untersuchungen neue Erkenntnisse, welche eine große Relevanz für die Diagnostik, Prognose und Therapie der PAH haben. Diese Ergebnisse könnten zur Entwicklung neuer, personalisierter Therapiestrategien führen. Zurzeit laufen mehrere Dutzend Phase-I- und Phase-II-Studien, in denen vielversprechende neue Substanzen geprüft werden.
Abstract
Pulmonary arterial hypertension (PAH) is a rare disease characterised by vascular remodelling of the small lung arteries leading to a decrease of the vessel lumen and eventually to occlusion. According to the current guidelines, PAH is defined by a pulmonary arterial pressure ≥ 25 mmHg, an arterial wedge pressure ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR > 3 WU). The current pathophysiological concepts include disturbances in the production, deposition and composition of the extracellular matrix, inflammatory processes, mutations in the BMPR2 gene as well as mutations in the KCNK3 gene. During the last few years, epigenetic and genetic investigations resulted in new findings which are highly relevant for the diagnosis, prognosis and therapy of PAH. These findings could lead to the development of new, individualised therapy strategies. Currently, several phase I and phase II studies are in progress, in which promising new substances are examined.
* Diese Autoren haben gleichermaßen zur Arbeit beigetragen.
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